General pharmaceutical chemistry. Pharmaceutical chemistry Professional activities of graduates

1. Introduction

1.1. The subject and content of pharmaceutical chemistry .......................................... ....... ................ 3

2.1. Modern problems and prospects for the development of pharmaceutical chemistry .............................................................. .............................................. ........ ...................... ...........................4

2.2. characteristics of the LS. Methods of obtaining them .............................................. . ........................5

2.3. Specific indicators of the quality of liquid, solid, soft and aseptically manufactured medicines .............................................................. .. ............................. ................6

2.4. Benignity L.S. Criteria for the good quality of HP .............................................. 8

2.5. Standardization L.S. Regulations......... .............................. ......... ............... ten

2.6. Causes of poor quality drugs .............................................................. ........... ......................eleven

2.7. LS stability. Expiration dates. Storage conditions.............. .............................. .... ...12

3.1. Conclusion.................... ............................. . ............................. ................... ........... .............fourteen

Bibliography.............................. .................. .............................................. ........ ..................fifteen

1. Introduction

1. Subject and content of pharmaceutical chemistry

Pharmaceutical chemistry is a science that studies the methods of preparation, structure, physical and chemical properties of medicinal substances, the relationship between their chemical structure and effects on the body, methods for controlling the quality of medicinal products and the changes that occur during their equation.

Methods for the study of medicinal substances:

These are dialectically closely related processes that complement each other. Analysis and synthesis are powerful means of understanding existing phenomena occurring in nature. Without analysis, there is no synthesis.

Knowledge of physics, mathematics and physio-biological disciplines is necessary for the knowledge of pharmaceutical chemistry. Strong knowledge of philosophy is also necessary, because Pharmaceutical chemistry, like other chemical sciences, deals with the study of the chemical form of the motion of matter.

Relationship of pharmaceutical chemistry with other sciences:

Pharmaceutical chemistry occupies one of the leading places among other special disciplines: pharmacology, drug manufacturing technology, toxicological chemistry, the organization of the economy of pharmacy and other pharmaceutical sciences and is a kind of link between them.

Pharmacognosy is a science that studies medicinal, plant materials. It creates the basis for the creation of new drugs from herbal medicinal raw materials.

Pharmacology is a science that studies the creation of new medicinal substances of drugs based on the methods of pharmaceutical chemistry (PC).

In the field of studying the relationship between the structure of the molecules of medicinal substances and their effect on the human body, PC also closely adjoins pharmacology.

Toxicological chemistry is based on the use of the same research methods as PC.

Drug technology - studies the methods of preparation of drugs that are objects for the development of pharmaceutical analysis methods, based on the study of the physical and chemical ingredients included in drugs, as well as the conditions for their storage when studying the processes occurring in manufactured drugs, establishes their shelf life, etc. .d.

In studying the issues of distribution and storage of medicines, as well as the organization of the control and analytical service, PH is closely related to the organization and economics of pharmacy.

PC occupies an intermediate position between the complex of biomedical and chemical sciences, the object of drug use is the body of a sick person.

The study of the processes occurring in the body of patients and their treatment is carried out by specialists working in the field of clinical medical sciences (doctors)

Pharmacists are engaged in the study of medicines, their analysis and synthesis.

II main part

2.1. Modern problems and prospects for the development of pharmaceutical chemistry

In our time, the issue of the actual creation and research of new drugs remains, despite the fact that we have a huge stock of available drugs, as well as the problem of finding new highly effective drugs.

The main problems of pharmaceutical chemistry are:

Creation and research of new drugs;

Development and research of new drugs;

Creation of safer drugs in connection with their side effects;

Prolonged use of drugs;

The evolution of microorganisms leads to the emergence of new diseases, the treatment of which requires effective drugs;

Despite the huge arsenal of available drugs, the problem of studying new, more highly effective drugs remains relevant. This is due to the lack or insufficiency of efficacy for the treatment of certain diseases, the presence of side effects, limited shelf life of drugs, or their dosage forms.

Sometimes a systemic update of some pharmacotherapeutic groups of drugs is simply necessary:

Antibiotics

Sulfonamides, since the microorganisms caused by the disease adapt to drugs, reducing their therapeutic activity.

It is promising to create new medicines both with the help of chemical or microbiological synthesis, and by isolating biologically active substances and plant and mineral raw materials.

Thus, the modern nomenclature of drugs in various pharmacotherapeutic groups requires further expansion. Created new drugs are promising only if they surpass existing ones in terms of their effectiveness and safety, and meet world requirements in terms of quality. In solving this problem, an important role belongs to specialists in the field of pharmaceutical chemistry, which reflects the social and medical significance of this science.

2.2. characteristics of the LS. Methods for obtaining them.

1.1 Characteristics of medicinal products.

Drug classification systems are used to describe the drug nomenclature of a country or region, and they create the prerequisites for national and international comparison of data on drug consumption, which must be collected and summarized in a unified way. Providing access to information on the use of medicines is necessary for auditing the structure of their consumption, identifying shortcomings in their use, initiating educational and other activities, as well as monitoring the final results of these activities.

Medicines are grouped according to the following principles:

1. Therapeutic use. For example, drugs for the treatment of tumors, lowering blood pressure, antimicrobials.

2. Pharmacological action, i.e. caused effect (vasodilators - expanding vessels, antispasmodics - eliminating vasospasm, analgesics - reducing pain irritation).

3. Chemical structure. Groups of drugs that are similar in structure. These are all salicylates derived from acetylsalicylic acid - aspirin, salicylamide, methyl salicylate, etc.

4. Nosological principle. A number of different drugs used to treat a well-defined disease (for example, drugs for the treatment of myocardial infarction, bronchial asthma, etc.

2.1 Methods for obtaining them.

1. Synthetic - medicinal substances obtained by targeted chemical reactions. (analgin, novocaine).

2. Semi-synthetic - obtained by processing natural raw materials:

Oil (paraffin, vaseline)

Coal (phenol, benzene)

Wood (tar)

3. Drugs obtained by distillation of medicinal plants are tinctures, extracts, vitamins, alkaloids, glycosides.

4. Inorganic drugs are raw materials from natural sources: NaCl - obtained from natural lakes, seas, CaCl - obtained from chalk or marble

5. Drugs of animal origin - obtained during the processing of organs and tissues of healthy animals from pig cattle (adrenaline, insulin, vitreous body)

6. Drugs of microbiological origin - isolated microorganisms (penicillins, cephalosporins) are used to obtain antibiotics. Great importance is attached to the synthesis of LP based on the study of metabolic products.

Metabolism is the transformation of substances introduced into the body in the process of metabolism carried out under the influence of various enzymes of the body and chemical relationships. The study of drug metabolism showed that some drugs have the ability to convert in the human body into more active substances (narcotic analgesics, codeine, and semi-synthetic heroin), metabolized into morphine, that is, a natural opium alkaloid.

2.3. Specific quality indicators of liquid, solid, soft and aseptically manufactured medicines.

Liquid drugs manufactured in pharmacies and manufactured by pharmaceutical companies include:

1. Solutions, incl. true solutions, colloidal solutions, solutions of high molecular weight compounds and from unlimited and limited swelling IUDs (high molecular weight compounds).
2. emulsions
3. Infusions and decoctions
4. Drops for internal and external use.
5. Liniments (liquid ointments)

In the vast majority of liquid drugs of factory and pharmacy manufacture, the dispersion medium is purified water. Sometimes high-quality fatty oils: sunflower, peach, olive.

In drugs for external use, other liquid media are also used: ethyl alcohol, glycerin, chloroform, diethyl ether, vaseline oil. GF 11th edition gives general articles on:

1. Eye drops
2. Injectable LF
3. Infusions and decoctions
4. Suspensions
5. emulsions
6. syrups
7. extracts

which regulate the quality of factory and pharmacy products.

OFS mandatory for manufacturers.

For this extensive group of drugs, quality indicators such as uniformity, absence of foreign mechanical impurities, transparency, for true solutions, compliance with color, taste, smell, and ND requirements are important.

In some cases, laboratories determine the density and viscosity of various types of solutions. One of the main indicators of the quality of true solutions is the refractive index, which can be used to determine the authenticity and purity of a drug and its quantitative content.

Powders are considered solid drugs. GF 11 includes Art. "Powders", which gives a description of this type of LF. Powders are intended for internal and external use. They consist of one or more crushed substances and have the property of flowability. Powders should be uniform when viewed with the naked eye.

Suppositories (solid drugs) - GF 11 characterizes them as solid at room temperature and melting dosed drugs at body temperature. Suppositories are used for introduction into body cavities, must have a homogeneous mass, without impurities and have a hardness for ease of use.

The general article suppositories in GF 11, in addition to the above quality indicators, also gives a number of other indicators that are determined in control and analytical laboratories, k.p. the time of complete deformation of the suppositories.

Tablets are solid drugs of factory production.

Soft drugs include ointments. GF 11 subdivides them into: ointments, pastes, creams, liniments. The main requirement for ointments: uniformity.

Eye ointments for b sterile. All types of factory and pharmacy products must be manufactured under conditions that prevent microbial contamination of drugs. This is especially true for solutions for injections, eye drops, powders for open wounds, and other dosage forms, which are produced and manufactured under the strictest aseptic conditions, so that as few organisms as possible get into the manufactured medicine. The fulfillment of this condition is checked by microbiological control. Pharmaceutical enterprises are equipped with special production facilities (workshops) in which sterile drugs are produced, and in pharmacies - in an aseptic unit, i.e. a set of rooms where aseptic conditions are strictly observed. The block includes: washing, distillation, sterilization, assistant and a number of other rooms. A set of premises.

Information on the specialty

The Department of Organic Chemistry of the Faculty of Chemistry and Technology trains graduates in the specialty 04.05.01 "Fundamental and Applied Chemistry", specializations "Organic Chemistry" and "Pharmaceutical Chemistry". The staff of the department - highly qualified teachers and researchers: 5 doctors of science and 12 candidates of chemical sciences.

Professional activity of graduates

Graduates are preparing for the following types of professional activities: research, research and production, teaching, design and organizational and managerial. A specialist chemist in the specialty "Fundamental and Applied Chemistry" will be ready to solve the following professional tasks: planning and setting work, which includes the study of the composition, structure and properties of substances and chemical processes, the creation and development of new promising materials and chemical technologies, the solution of fundamental and applied problems in the field of chemistry and chemical technology; preparation of a report and scientific publications; scientific and pedagogical activity at a university, at a secondary specialized educational institution, at a secondary school. Successful students engaged in scientific work can undergo an internship, take part in scientific conferences, olympiads and competitions of various levels, as well as submit the results of scientific work for publication in Russian and foreign scientific journals. Students have at their disposal chemical laboratories equipped with modern equipment and a computer class with the necessary literature and access to full-text electronic databases.

Specialists will:

• master the skills of a chemical experiment, basic synthetic and analytical methods for obtaining and studying chemicals and reactions;
• present the main chemical, physical and technical aspects of chemical industrial production, taking into account raw materials and energy costs;
• have the skills to work on modern educational and scientific equipment when conducting chemical experiments;
• have experience in working on serial equipment used in analytical and physico-chemical studies (gas-liquid chromatography, infrared and ultraviolet spectroscopy);
• own the methods of registration and processing of the results of chemical experiments.
• Possess the skills of planning, staging and conducting chemical experiments in the field of fine organic synthesis to obtain substances with desired useful properties

Students acquire knowledge in the field of fundamentals of inorganic chemistry, organic chemistry, physical and colloidal chemistry, analytical chemistry, planning of organic synthesis, chemistry of alicyclic and framework compounds, catalysis in organic synthesis, chemistry of organoelement compounds, pharmaceutical chemistry, modern methods of analysis and quality control of medicines , Fundamentals of Medicinal Chemistry, Fundamentals of Pharmaceutical Technology, Fundamentals of Pharmaceutical Analysis. In the course of practical classes, students gain skills in working in a modern chemical laboratory, master methods for obtaining and analyzing new compounds. Students have the skills to work on a gas-liquid chromatograph, infrared spectrophotometer, ultraviolet spectrophotometer. Students undergo in-depth study of a foreign language (for 3 years).

In the process of learning, students master the methods of working on the analytical equipment of the Department of Organic Chemistry:

Chromato-mass spectrometer Finnigan Trace DSQ

NMR spectrometer JEOL JNM ECX-400 (400 MHz)

HPLC/MS with high resolution time-of-flight mass spectrometer with ESI and DART ionization source, with diode array and fluorimetric detectors

Reveleris X2 Preparative Flash Chromatography System with UV and ELSD Detectors

Shimadzu IR Affinity-1 FT-IR Spectrometer

Waters Liquid Chromatograph with UV and Refractometric Detectors

TA Instruments DSC-Q20 Differential Scanning Calorimeter

Automatic C,H,N,S analyzer EuroVector EA-3000

Scanning spectrofluorimeter Varian Cary Eclipse

Automatic polarimeter AUTOPOL V PLUS

OptiMelt Automatic Melting Pointer

High Performance Computing Station

The training process provides for familiarization and chemical-technological practices in the laboratories of enterprises:

• CJSC "All-Russian Research Institute of Organic Synthesis of NK";
• JSC "Middle Volga Research Institute for Oil Refining" NK Rosneft;
• CJSC "TARKETT";
• Samara CHPP;
• OAO Syzransky Refinery Rosneft Oil Company;
• JSC "Giprovostokneft";
• OJSC Aviation Bearings Plant;
• OOO Novokuibyshevsky Plant of Oils and Additives, Rosneft Oil Company;
• CJSC "Neftekhimiya"
• LLC "Pranafarm"
• OOO "Ozon"
• JSC Electroshield
• FSUE GNPRKTS
• TsSKB-Progress
• OJSC "Baltika"
• PJSC SIBUR Holding, Togliatti

Successful students engaged in scientific work can undergo internships, take part in scientific conferences, olympiads and competitions of various levels, as well as submit the results of scientific work for publication in Russian and foreign scientific journals. Specialists who have received training in the specialty "Fundamental and Applied Chemistry" are in demand in the laboratories of state scientific centers and private companies, in research and analytical laboratories of various industries (chemical, food, metallurgical, pharmaceutical, petrochemical and gas production), in forensic laboratories; in customs laboratories; diagnostic centers; sanitary and epidemiological stations; environmental control organizations; certification testing centers; enterprises of the chemical industry, ferrous and non-ferrous metallurgy; in educational institutions of the system of secondary vocational education; departments of labor protection and industrial sanitation; meteorological stations.

Qualification "Chemist. Chemistry teacher" with a specialization in "Organic Chemistry" or "Pharmaceutical Chemistry". Enrollment based on the results of the Unified State Examination: chemistry, mathematics and Russian. Duration of study: 5 years (full-time). Possible admission to graduate school.

Subject and tasks of pharmaceutical chemistry.

Pharmaceutical chemistry (PC) is a science that studies methods of obtaining,

structures, physical and chemical properties of medicinal substances; the relationship between their chemical structure and action on the body; methods of quality control of medicines and changes occurring during their storage. The problems facing it are solved with the help of physical, chemical and physico-chemical research methods used both for the synthesis and for the analysis of medicinal substances. PC is based on the theory and laws of related chemical sciences: inorganic, organic, analytical, physical and biological chemistry. It is closely related to pharmacology, biomedical and clinical disciplines.

Terminology in FH

The object of study of PC are pharmacological and medicinal products. The first of these is a substance or mixture of substances with established pharmacological activity, which is the object of clinical trials. After conducting clinical trials and obtaining positive results, the drugs are approved by the Pharmacological and Pharmacopeial Committees for use and receive the name of the drug. A medicinal substance is a substance that is an individual chemical compound or biological substance. A dosage form is a convenient state for use, given to a drug, in which the desired therapeutic effect is achieved. It includes powders, tablets, solutions, ointments, suppositories. A dosage form manufactured by a particular company and given a brand name is called a drug.

Sources of medicines

Medicinal substances by their nature are divided into inorganic and organic. They can be obtained from natural sources and synthetically. Rocks, gases, sea water, production wastes, etc. can be raw materials for obtaining inorganic substances. Organic medicinal substances are obtained from oil, coal, oil shale, gases, tissues of plants, animals, microorganisms, and other sources. In recent decades, the number of drugs obtained synthetically has increased dramatically.

Often, the complete chemical synthesis of many compounds (alkaloids, antibiotics, glycosides, etc.) is technically complex and new methods for obtaining drugs are used: semi-synthesis, biosynthesis, genetic engineering, tissue culture, etc. With the help of semi-synthesis, drugs are obtained from intermediates of natural origin, for example semi-synthetic penicillins, cephalosporins, etc. Biosynthesis is a natural synthesis of the final product by living organisms based on natural intermediates.

The essence of genetic engineering is to change the genetic programs of microorganisms by introducing into their DNA genes encoding the biosynthesis of certain drugs, such as insulin. Tissue culture is the reproduction in artificial conditions of animal or plant cells, which become raw materials for the production of drugs. For the development of the latter, hydrobionts, plant and animal organisms of the seas and oceans are also used.

Classification of medicinal substances.

There are two types of classification of a large number of medicinal substances used: pharmacological and chemical. The first of them divides medicinal substances into groups depending on the mechanism of action on individual organs and systems of the body (central nervous, cardiovascular, digestive, etc.). This classification is convenient for use in medical practice. Its disadvantage is that in one group there may be substances with different chemical structures, which makes it difficult to unify the methods of their analysis.

According to the chemical classification, medicinal substances are divided into groups based on the commonality of their chemical structure and chemical properties, regardless of the pharmacological action. For example, pyridine derivatives have different effects on the body: nicotinamide is a vitamin PP, nicotinic acid diethylamide (cordiamin) stimulates the central nervous system, etc. Chemical classification is convenient because it allows you to identify the relationship between the structure and mechanism of action of medicinal substances, and also allows you to unify the methods of their analysis. In some cases, a mixed classification is used to take advantage of the pharmacological and chemical classification of drugs.

requirements for medicines.

The quality of a medicinal product is determined by its appearance, solubility, identification of its authenticity, degree of purity and quantitative determination of the content of a pure substance in the preparation. The complex of these indicators is the essence of pharmaceutical analysis, the results of which must comply with the requirements of the State Pharmacopoeia (SP).

The authenticity of the medicinal substance (confirmation of its identity) is established using chemical, physical and physico-chemical research methods. Chemical methods include reactions to the functional groups included in the structure of the drug, which are characteristic of a given substance: According to the Global Fund, they are reactions to aromatic primary amines, ammonium, acetates, benzoates, bromide, bismuth, ferrous and oxide iron, iodides, potassium, calcium, carbonates (bicarbonates), magnesium, arsenic, sodium, nitrates, nitrites, oxide mercury, salicylates, sulfates, sulfites, tartrates, phosphates, chlorides, zinc and citrates.

Physical methods for establishing the authenticity of a medicinal product include determining its: 1) physical properties: state of aggregation, color, odor, taste, crystal shape or type of amorphous substance, hygroscopicity or degree of weathering in air, volatility, mobility and flammability and 2) physical constants: temperatures melting (decomposition) and solidification, density, viscosity, solubility in water and other solvents, transparency and degree of turbidity, color, ash, insoluble in hydrochloric acid and sulfate and volatile substances and water.

Physical and chemical methods for studying authenticity consist in the use of instruments for chemical analysis: spectrophotometers, fluorometers, flame photometers, chromatography equipment, etc.

Impurities in medicines and their sources.

Many drugs contain certain impurities of foreign substances. Exceeding their level may cause unwanted action. The reasons for the ingress of impurities into medicinal substances may be insufficient purification of the feedstock, by-products of synthesis, mechanical contamination, impurities of the materials from which the equipment is made, and violation of storage conditions.

The GF requires either a complete absence of impurities, or allows a maximum allowable limit of them defined for a given drug, which does not affect the quality and therapeutic effect of the drug. Reference solutions are provided to determine the acceptable limit of HF impurities. The result of a reaction to a particular impurity is compared with the result of a reaction carried out with the same reagents and in the same volume with a reference, standard solution containing an acceptable amount of impurity. Determining the degree of purity of a medicinal product includes testing for: chlorides, sulfates, ammonium salts, calcium, iron, zinc, heavy metals and arsenic.

region. State Pharmacopoeia of the USSR (SF USSR)

The GF of the USSR is a collection of obligatory national standards and regulations that regulate the quality of medicinal substances. It is based on the principles of Soviet healthcare and reflects modern achievements in the field of pharmacy, medicine, chemistry and other related sciences. The Soviet pharmacopoeia is a national document, it reflects the social essence of Soviet health care, the level of science and culture of the population of our country. The State Pharmacopoeia of the USSR has a legislative character. Its requirements for medicines are obligatory for all enterprises and institutions of the Soviet Union that manufacture, store, control quality and use medicines.

The first edition of the Soviet Pharmacopoeia, called the VII edition of the State Pharmacopoeia of the USSR (SP VII), was put into effect in July 1926. A. E. Chichibabina. The First Soviet Pharmacopoeia differed from previous editions in its increased scientific level, the desire for a possible replacement of medicines made from imported raw materials with domestically produced medicines. Higher requirements were imposed in GF VII not only for drugs, but also for products used for their manufacture.

Based on these principles, 116 articles for new drugs were included in GF VII and 112 articles were excluded. Significant changes have been made to the requirements for drug quality control. A number of new methods of chemical and biological standardization of drugs were provided, 30 general articles were included in the form of appendices, descriptions of some general reactions used to determine the quality of drugs, etc. were given. The organoleptic control of many drugs was for the first time replaced by more objective physical and chemical methods, biological control methods were introduced.

Thus, in GF VII, priority was given to improving the quality control of medicines. This principle was further developed in subsequent editions of the pharmacopoeias.

In 1949, the VIII edition was published, and in October 1961, the IX edition of the State Pharmacopoeia of the USSR. By this time, new groups of highly effective drugs (sulfonamides, antibiotics, psychotropic, hormonal and other drugs) had been created, which required the development of new methods of pharmaceutical analysis.

The X edition of the State Pharmacopoeia (SP X) was put into effect on July 1, 1969. It reflected the new achievements of the domestic pharmaceutical and medical science and industry.

The fundamental difference between GF IX and GF X is the transition to a new international terminology of drugs, as well as a significant update of both the nomenclature and methods of drug quality control.

In SP X, the requirements for the quality of medicines have been significantly increased, the methods of pharmacopoeial analysis have been improved, and the scope of physical and chemical methods has been expanded. Numerous general articles, reference tables and other materials included in SP X reflected the requirements necessary for assessing the qualitative and quantitative characteristics of medicines.

The State Pharmacopoeia of the USSR X edition includes 4 parts: "Introductory part"; "Preparations" (private and group articles); "General methods of physico-chemical, chemical and biological research"; "Applications".

The "Introductory part" sets out the general principles of construction and the procedure for using SP X, the compilers, changes that distinguish SP X from SP IX, list A and list B of medicinal substances are indicated.

GF X contains 707 articles for medicinal substances (in GF IX there were 754) and 31 group articles (in GF IX there were 27). The nomenclature was updated by 30% due to the exclusion of drugs that were discontinued from production, as well as having limited use. The quality of the latter is established in accordance with the requirements of GF IX.

Compared to SP IX, the number of individual (synthetic and natural) medicines increased from 273 to 303, from 10 to 22 antibiotics, for the first time radioactive preparations were included in SP X. Among the drugs included in the GF X are new cardiovascular, psychotropic, ganglioblocking, antimalarial, anti-tuberculosis drugs, drugs for the treatment of malignant neoplasms, fungal diseases, new drugs for anesthesia, hormonal drugs, vitamins. Most of them were obtained for the first time in our country.

"Preparations" - the main part of SP X (pp. 39-740). 707 articles set out the requirements for the quality of medicines (quality standards). Each medicinal product, in accordance with the requirements of the pharmacopoeia, is subjected to physical properties testing, identity testing, purity testing and determination of the quantitative content of the drug. In GF X, the structure of articles reflecting the sequence of control is detailed. The "Properties" section has been replaced by two sections: "Description" and "Solubility". The description of authenticity reactions for 25 ions and functional groups is summarized in one general article, and references are given to it in private articles.

Changed the order of articles. For the first time in SP X, articles on finished dosage forms are located after articles on the corresponding medicinal product. In most articles of GF X there is a heading indicating the pharmacological action of the drug. Detailed information about the highest doses of drugs for various methods of administration.

The third part of SP X "General Methods of Physicochemical, Chemical and Biological Research" provides a brief description of the methods used for pharmacopoeial analysis, provides information on reagents, titrated solutions and indicators.

"Appendices" to SP X contain reference tables of atomic masses, densities, constants (solvents, acids, bases) and other quality indicators of drugs. This also includes tables of higher single and daily doses of poisonous and potent drugs for adults, children, and also for animals.

After the release of the 10th edition of the State Pharmacopoeia, the Ministry of Health of the USSR approved a number of new highly effective drugs for use in medical practice. Many of them were first developed by scientists of our country. At the same time, ineffective drugs were excluded, which were replaced by more modern drugs. Therefore, there is a need to create a new XI edition of the State Pharmacopoeia of the USSR, which is being prepared at the present time. Scientific institutions and enterprises of the USSR Ministry of Public Health, the Ministry of Medical Industry and other departments are involved in this work. The new State Pharmacopoeia will reflect modern achievements in the field of pharmaceutical analysis and improvement of the quality of medicines.

National and regional pharmacopoeias

Such large capitalist states as the USA, Great Britain, France, Germany, Japan, Italy, Switzerland and some others systematically produce national pharmacopoeias every 5-8 years. Published in 1924-1946. the pharmacopoeias of Greece, Chile, Paraguay, Portugal, Venezuela have already lost their significance.

Along with pharmacopoeias, in some countries, collections of official requirements for medicines such as the US National Formulary, the British Pharmaceutical Code are periodically published. They standardize the quality of new drugs that are not included in the pharmacopoeias or included in earlier editions of the pharmacopoeias.

The first experience of creating a regional pharmacopeia was carried out by the Scandinavian countries (Norway, Finland, Denmark and Sweden). The published Scandinavian pharmacopoeia since 1965 has acquired a legislative character for these countries.

Eight Western European states (Great Britain, Germany, France, Italy, Belgium, Luxembourg, the Netherlands and Switzerland), members of the EEC (European Economic Community), created in 1964 a pharmacopoeial commission. She prepared and in 1969 published the first, and in 1971 the second volume of the EEC Pharmacopoeia (in 1973, an addition to these editions was issued). In 1976, the EEC Pharmacopoeia was recognized by the Scandinavian countries, Iceland and Ireland. The EEC Pharmacopoeia is of a legislative nature, but does not replace the national pharmacopoeias of these countries.

Regional pharmacopoeias contribute to the unification of the nomenclature and quality requirements for medicines obtained in different countries

Quality control of medicines in pharmacies

Intra-pharmacy drug quality control includes not only analytical control, but also a system of measures that ensure the correct storage, preparation and dispensing of drugs. It is based on strict adherence to the pharmaceutical and sanitary regime in the pharmacy. It is especially necessary to carefully follow the rules for storing medicines, the technology for preparing injection solutions, concentrates and eye drops.

For intra-pharmacy quality control of medicines, pharmacies should have analytical rooms or analytical tables equipped with the necessary instruments, reagents, reference and special literature. Intra-pharmacy control is carried out by pharmacists-analysts who are part of the staff of large pharmacies, as well as pharmacists-technologists, whose duties include checking the quality of medicines. They have an equipped workplace on the assistant's table or next to it. The head of the pharmacy and his deputies manage the quality control of medicines. They must own all types of intra-pharmacy control, and in small pharmacies themselves perform the functions of a pharmacist-analyst or pharmacist-technologist.

Direct analytical control in a pharmacy includes three main areas: quality control of medicinal substances coming from industry, quality control of distilled water, and various types of quality control of dosage forms manufactured in a pharmacy.

Medicinal substances entering the pharmacy from the industry, regardless of the presence of the OTC stamp, are controlled for identity. Preparations that rapidly change during storage are sent at least once a quarter for testing to control and analytical laboratories.

Systematic monitoring of the good quality of distilled water in a pharmacy ensures the quality of preparation of all liquid dosage forms. Therefore, distilled water is controlled in each cylinder for the absence of chlorides, sulfates and calcium salts. Even higher requirements are imposed on the water used for the preparation of injection solutions. Its absence of reducing substances, ammonia, carbon dioxide. At least once a quarter, the pharmacy sends distilled water for a complete analysis to the control and analytical laboratory, and twice a year to the sanitary and bacteriological laboratory to check the absence of microflora contamination.

All dosage forms manufactured in pharmacies are subject to intra-pharmacy control. There are several types of control: written, organoleptic, questionnaire, physical and chemical. Written, organoleptic, questioning and physical control is carried out, as a rule, by a pharmacist-technologist after the pharmacist has manufactured at least 5 medicines, and chemical control is carried out by a pharmacist-analyst.

All drugs manufactured in any pharmacy are subject to written control. The essence of written control is that the pharmacist, after preparing the medicine, writes down from memory on a special form the name and total weight of each ingredient or indicates the content of each concentrate taken. Then the form, together with the prescription, is submitted for verification to the pharmacist-technologist. The completed forms are stored in the pharmacy for 12 days.

Organoleptic control includes checking the appearance (color, uniformity of mixing), smell and taste of drugs, the absence of mechanical impurities. All medicines prepared for internal use by children and selectively prepared for adults are checked for taste (excluding medicines containing ingredients related to list A).

Questioning control is carried out by a pharmacist-technologist. He names the ingredient, and in compound medicines the content of the first ingredient. After that, the pharmacist calls all the other ingredients and their quantities. If concentrates were used to make the medicine, the pharmacist lists them with an indication of the percentage. Questionnaire control is carried out immediately after the manufacture of medicines, if they are intended for injection or they contain list A drugs. If there is doubt about the quality of the manufactured medicine, questioning control is an additional type of control.

Physical control consists in checking the total volume (mass) of the prepared drug or the mass of its individual doses. Controlled 5-10% of the number of doses prescribed in the prescription, but not less than three doses. Physical control is carried out selectively, periodically throughout the working day. Together with physical control, the correctness check is carried out, the correctness of the design of drugs and the compliance of the packaging with the physical and chemical properties of the ingredients that make up the dosage form are carried out.

Chemical control includes qualitative and quantitative chemical analysis of medicines prepared in a pharmacy. All injection solutions are subjected to qualitative chemical analysis (before they are sterilized); eye drops; each series of concentrates, semi-finished products and in-pharmaceutical preparations; medicines coming from the stock department to the assistant department; children's dosage forms; drugs containing list A drugs. Selectively control drugs made from individual impurities.

To perform a qualitative analysis, the drop method is mainly used, using tables of the most characteristic reactions.

th practical work requires the study of the basics of general pharmaceutical chemistry and methods for studying the qualitative and quantitative study of substances most commonly found in veterinary practice.

The list of medicines subject to quantitative analysis depends on the availability of a pharmacist-analyst in the pharmacy. If it is in the state of the pharmacy, then all drugs for injection are subjected to quantitative analysis (before sterilization); eye drops (containing silver nitrate, atropine sulfate, dicaine, ethylmorphine pilocarpine hydrochloride); solutions of atropine sulfate for internal use; all concentrates, semi-finished products and in-pharmaceutical preparations. The remaining drugs are analyzed selectively, but daily by each pharmacist. First of all, they control medicines used in pediatric and ophthalmic practice, as well as those containing preparations of list A. Perishable medicines (solutions of hydrogen peroxide, ammonia and formaldehyde, lime water, ammonia-anise drops) are analyzed at least once a quarter.

If there is no pharmacist-analyst, but there are two or more pharmacists in the pharmacy staff, then injection solutions (before sterilization) containing novocaine, atropine sulfate, calcium chloride, sodium chloride, glucose are subjected to quantitative analysis; eye drops containing silver nitrate, atropine sulfate, pilocarpine hydrochloride; all concentrates; hydrochloric acid solutions. Perishable medicines from these pharmacies are sent for testing to control and analytical laboratories.

Injectable solutions containing novocaine and sodium chloride are subject to qualitative and quantitative analysis in category VI pharmacies with one pharmacist in the state and in pharmacy points of the first group; eye drops containing atropine sulfate and silver nitrate.

The procedure for assessing the quality of drugs manufactured in pharmacies and the norms of permissible deviations in the manufacture of drugs are established by order of the Ministry of Health of the USSR No. 382 dated September 2, 1961. To assess the quality of manufactured drugs, the terms are used: “satisfies” or “does not satisfy” the requirements of the USSR GF, FS , VFS or instructions of the Ministry of Health of the USSR.

Features of pharmaceutical analysis.

Pharmaceutical analysis is one of the main branches of pharmaceutical chemistry. It has its own specific features that distinguish it from other types of analysis. They consist in the fact that substances of various chemical nature are subjected to research: inorganic, element-organic, radioactive, organic compounds from simple aliphatic to complex natural biologically active substances. The range of concentrations of analytes is extremely wide. The objects of pharmaceutical research are not only individual medicinal substances, but also mixtures containing a different number of components. The number of medicines used is increasing every year. This leads to the need for both the development of new methods of analysis and the unification of already known ones.

The continuous increase in the requirements for the quality of medicines dictates the need for continuous improvement of pharmaceutical analysis. Moreover, the requirements are growing both for the good quality of medicinal substances and for the quantitative content. This necessitates the widespread use of not only chemical, but also more sensitive physical and chemical methods for assessing the quality of drugs.

The requirements for pharmaceutical analysis are high. It should be sufficiently specific and sensitive, accurate in relation to the standards stipulated by the USSR GF, VFS, FS and other NTD, carried out in short periods of time using the minimum quantities of tested drugs and reagents.

Pharmaceutical analysis, depending on the tasks, includes various forms of drug quality control: pharmacopoeial analysis, step-by-step control of the production of medicines, analysis of individual dosage forms, express analysis in a pharmacy, and biopharmaceutical analysis.

Pharmacopoeial analysis is an integral part of pharmaceutical analysis. It is a set of methods for studying drugs and dosage forms set forth in the State Pharmacopoeia or other regulatory and technical documentation (VFS, FS). Based on the results obtained during the pharmacopoeial analysis, a conclusion is made on the compliance of the medicinal product with the requirements of the USSR GF or other regulatory and technical documentation. In case of deviation from these requirements, the drug is not allowed to be used.

Performing a pharmacopoeial analysis allows you to establish the authenticity of the drug, its good quality, to determine the quantitative content of the pharmacologically active substance or ingredients that make up the dosage form. While each of these steps has a specific purpose, they cannot be considered in isolation. They are interrelated and complement each other. For example, melting point, solubility, pH of an aqueous solution, etc. are criteria for both the authenticity and the good quality of the medicinal substance.

SP X describes the methods of appropriate tests in relation to one or another pharmacopoeial preparation. Many of these methods are identical. To summarize a large amount of private information on pharmacopoeial analysis, the main criteria for pharmaceutical analysis and the general principles of testing for authenticity, good quality and quantitative determination of medicinal substances will be considered. In separate sections, the state of and prospects for the use of physicochemical and biological methods in the analysis of drugs are considered.

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Pharmaceutical chemistry and pharmaceutical analysis

Introduction

1. Characteristics of pharmaceutical chemistry as a science

1.1 Subject and tasks of pharmaceutical chemistry

1.2 Relationship of pharmaceutical chemistry with other sciences

1.3 Pharmaceutical chemistry objects

1.4 Modern problems of pharmaceutical chemistry

2. History of development of pharmaceutical chemistry

2.1 The main stages in the development of pharmacy

2.2 Development of pharmaceutical chemistry in Russia

2 .3 Development of pharmaceutical chemistry in the USSR

3. Pharmaceutical analysis

3.1 Basic principles of pharmaceutical and pharmacopoeial analysis

3.2 Pharmaceutical Analysis Criteria

3.3 Mistakes during Pharmaceutical Analysis

3.4 General principles for testing the authenticity of medicinal substances

3.5 Sources and causes of poor quality of medicinal substances

3.6 General requirements for purity testing

3.7 Methods for studying the quality of medicines

3.8 Validation of methods of analysis

findings

List of used literature

Introduction

Among the tasks of pharmaceutical chemistry - such as modeling new drugs, drugs and their synthesis, the study of pharmacokinetics, etc., the analysis of the quality of drugs occupies a special place. The State Pharmacopoeia is a collection of mandatory national standards and regulations that normalize the quality of drugs.

Pharmacopoeial analysis of medicines includes quality assessment for a variety of indicators. In particular, the authenticity of the medicinal product is established, its purity is analyzed, and a quantitative determination is carried out. Initially, only chemical methods were used for such analysis; authenticity tests, impurity reactions and titration in quantitation.

Over time, not only the level of technical development of the pharmaceutical industry has increased, but also the requirements for the quality of medicines have changed. In recent years, there has been a trend towards a transition to the extended use of physical and physico-chemical methods of analysis. In particular, spectral methods are widely used - infrared and ultraviolet spectrophotometry, nuclear magnetic resonance spectroscopy, etc. Chromatography methods (high-performance liquid, gas-liquid, thin-layer), electrophoresis, etc. are actively used.

The study of all these methods and their improvement is one of the most important tasks of pharmaceutical chemistry today.

1. Characteristics of pharmaceutical chemistry as a science

1.1 Subject and tasks of pharmaceutical chemistry

Pharmaceutical chemistry is a science that, based on the general laws of chemical sciences, explores the methods of obtaining, structure, physical and chemical properties of medicinal substances, the relationship between their chemical structure and effect on the body, quality control methods and changes that occur during storage.

The main methods for the study of medicinal substances in pharmaceutical chemistry are analysis and synthesis - dialectically closely related processes that complement each other. Analysis and synthesis are powerful means of understanding the essence of phenomena occurring in nature.

The tasks facing pharmaceutical chemistry are solved using classical physical, chemical and physicochemical methods, which are used both for the synthesis and for the analysis of medicinal substances.

To learn pharmaceutical chemistry, the future pharmacist must have deep knowledge in the field of general theoretical chemical and biomedical disciplines, physics, and mathematics. Strong knowledge in the field of philosophy is also necessary, because pharmaceutical chemistry, like other chemical sciences, deals with the study of the chemical form of the motion of matter.

1.2 Relationship of pharmaceutical chemistry with other sciences

Pharmaceutical chemistry is an important branch of chemical science and is closely related to its individual disciplines (Fig. 1). Using the achievements of basic chemical disciplines, pharmaceutical chemistry solves the problem of targeted search for new drugs.

For example, modern computer methods make it possible to predict the pharmacological action (therapeutic effect) of a drug. A separate direction has been formed in chemistry associated with the search for one-to-one correspondences between the structure of a chemical compound, its properties and activity (QSAR-, or KKSA-method - quantitative structure-activity correlation).

The relationship "structure - property" can be detected, for example, by comparing the values ​​of the topological index (an indicator that reflects the structure of the medicinal substance) and the therapeutic index (the ratio of the lethal vine to the effective dose LD50/ED50).

Pharmaceutical chemistry is also related to other, non-chemical disciplines (Fig. 2).

So, knowledge of mathematics allows, in particular, to apply the metrological assessment of the results of the analysis of drugs, computer science provides timely receipt of information about drugs, physics - the use of fundamental laws of nature and the use of modern equipment in analysis and research.

There is an obvious relationship between pharmaceutical chemistry and special disciplines. The development of pharmacognosy is impossible without the isolation and analysis of biologically active substances of plant origin. Pharmaceutical analysis accompanies individual stages of technological processes for obtaining drugs. Pharmacoeconomics and pharmacy management come into contact with pharmaceutical chemistry when organizing a system for standardization and quality control of medicines. Determination of the content of drugs and their metabolites in biological media in equilibrium (pharmacodynamics and toxicodynamics) and in time (pharmacokinetics and toxicokinetics) demonstrates the possibilities of using pharmaceutical chemistry to solve problems of pharmacology and toxicological chemistry.

A number of disciplines of biomedical profile (biology and microbiology, physiology and pathophysiology) represent the theoretical basis for the study of pharmaceutical chemistry.

A close relationship with all of these disciplines provides a solution to modern problems of pharmaceutical chemistry.

Ultimately, these problems come down to the creation of new, more effective and safe drugs and the development of methods for pharmaceutical analysis.

1.3 Pharmaceutical chemistry facilities

The objects of pharmaceutical chemistry are extremely diverse in terms of chemical structure, pharmacological action, mass, number of components in mixtures, the presence of impurities and related substances. These objects include:

Medicinal substances (LM) -- (substances) are individual substances of plant, animal, microbial or synthetic origin that have pharmacological activity. Substances are intended for obtaining medicines.

Medicines (PM) are inorganic or organic compounds with pharmacological activity, obtained by synthesis, from plant materials, minerals, blood, blood plasma, organs, tissues of a human or animal, as well as using biological technologies. Drugs also include biologically active substances (BAS) of synthetic, plant or animal origin, intended for the production or manufacture of medicines. Dosage form (DF) -- attached to the drug or MPC convenient for use in the state in which the desired therapeutic effect is achieved.

Medicinal preparations (MP) - dosed drugs in a specific LF, ready for use.

All of the indicated drugs, drugs, drug products and drugs can be both domestic and foreign-made, approved for use in the Russian Federation. The given terms and their abbreviations are official. They are included in the OSTs and are intended for use in pharmaceutical practice.

The objects of pharmaceutical chemistry also include starting products used to obtain drugs, intermediate and by-products of synthesis, residual solvents, excipients and other substances. In addition to patented drugs, the objects of pharmaceutical analysis are generics (generic drugs). For the developed original drug, the pharmaceutical manufacturing company receives a patent, which confirms that it is the property of the company for a certain period (usually 20 years). The patent provides the exclusive right to implement it without competition from other manufacturers. After the expiration of the patent, the free production and sale of this drug is allowed to all other companies. It becomes a generic drug, or generic, but must be absolutely identical to the original. The difference is only in the difference in the name given by the manufacturer. A comparative evaluation of a generic and original drug is carried out according to pharmaceutical equivalence (equal content of the active ingredient), bioequivalence (equal concentrations of accumulation when taken in the blood and tissues), therapeutic equivalence (the same efficacy and safety when administered under equal conditions and doses). The advantages of generics are a significant reduction in costs compared to the creation of the original drug. However, their quality is assessed in the same way as the corresponding original drugs.

The objects of pharmaceutical chemistry are also various finished medicinal products (FPP) of the factory and dosage forms of pharmaceutical production (DF), medicinal plant raw materials (MP). These include tablets, granules, capsules, powders, suppositories, tinctures, extracts, aerosols, ointments, plasters, eye drops, various injectable dosage forms, ophthalmic medicinal films (OMFs). The content of these and other terms and concepts is given in the terminological dictionary of this textbook.

Homeopathic medicines are single- or multi-component medicinal products containing, as a rule, microdoses of active compounds produced according to a special technology and intended for oral, injection or topical use in the form of various dosage forms.

An essential feature of the homeopathic method of treatment is the use of small and ultra-low doses of drugs, prepared by stepwise serial dilution. This determines the specific features of the technology and quality control of homeopathic medicines.

The range of homeopathic drugs consists of two categories: monocomponent and complex. For the first time, homeopathic drugs were included in the State Register in 1996 (in the amount of 1192 monopreparations). Subsequently, this nomenclature expanded and now includes, in addition to 1192 monopreparations, 185 domestic and 261 foreign homeopathic drugs. Among them are 154 substances-tinctures of matrix, as well as various dosage forms: granules, sublingual tablets, suppositories, ointments, creams, gels, drops, injection solutions, lozenges for resorption, oral solutions, patches.

Such a large range of homeopathic dosage forms requires high quality requirements. Therefore, their registration is carried out in strict accordance with the requirements of the licensing system, as well as for allopathic drugs with subsequent registration with the Ministry of Health. This provides a reliable guarantee of the effectiveness and safety of homeopathic drugs.

Biologically active food additives (BAA) (nutraceuticals and parapharmaceuticals) are concentrates of natural or identical biologically active substances intended for direct intake or introduction into food products in order to enrich the human diet. BAA is obtained from vegetable, animal or mineral raw materials, as well as by chemical and biotechnological methods. Dietary supplements include bacterial and enzyme preparations that regulate the microflora of the gastrointestinal tract. Dietary supplements are produced at food, pharmaceutical and biotechnological enterprises in the form of extracts, tinctures, balms, powders, dry and liquid concentrates, syrups, tablets, capsules and other forms. Pharmacies and diet food stores sell dietary supplements. They should not contain strong, narcotic and poisonous substances, as well as VP, not used in medicine and not used in food. Expert assessment and hygienic certification of dietary supplements is carried out in strict accordance with the regulation approved by Order No. 117 of April 15, 1997 “On the procedure for examination and hygienic certification of biologically active food supplements”.

For the first time dietary supplements appeared in medical practice in the United States in the 60s. 20th century Initially, they were complexes consisting of vitamins and minerals. Then they began to include various components of plant and animal origin, extracts and powders, incl. exotic natural products.

When compiling dietary supplements, the chemical composition and dosages of components, especially metal salts, are not always taken into account. Many of them can cause complications. Their effectiveness and safety are not always studied in sufficient volume. Therefore, in some cases, dietary supplements can do harm instead of good, because. their interaction with each other, dosages, side effects, and sometimes even narcotic effects are not taken into account. In the United States from 1993 to 1998, 2621 reports of adverse reactions to dietary supplements were registered, incl. 101 fatalities. Therefore, the WHO decided to tighten control over dietary supplements and impose requirements on their effectiveness and safety similar to the criteria for the quality of medicines.

1.4 Modern problems of pharmaceutical chemistry

The main problems of pharmaceutical chemistry are:

* creation and research of new medicines;

* development of methods for pharmaceutical and biopharmaceutical analysis.

Creation and research of new drugs. Despite the huge arsenal of available drugs, the problem of finding new highly effective drugs remains relevant.

The role of drugs is constantly growing in modern medicine. This is due to a number of reasons, the main ones being:

ѕ a number of serious diseases are not yet cured by drugs;

* long-term use of a number of drugs forms tolerant pathologies, to combat which new drugs with a different mechanism of action are needed;

* the processes of evolution of microorganisms lead to the emergence of new diseases, the treatment of which requires effective drugs;

* some of the drugs used cause side effects, and therefore it is necessary to create safer drugs.

The creation of each new original drug is the result of the development of fundamental knowledge and achievements of medical, biological, chemical and other sciences, intensive experimental research, and the investment of large material costs. The successes of modern pharmacotherapy were the result of deep theoretical studies of the primary mechanisms of homeostasis, the molecular basis of pathological processes, the discovery and study of physiologically active compounds (hormones, mediators, prostaglandins, etc.). Achievements in the study of the primary mechanisms of infectious processes and the biochemistry of microorganisms contributed to the development of new chemotherapeutic agents. The creation of new drugs turned out to be possible on the basis of achievements in the field of organic and pharmaceutical chemistry, the use of a complex of physicochemical methods, and technological, biotechnological, biopharmaceutical and other studies of synthetic and natural compounds.

The future of pharmaceutical chemistry is connected with the demands of medicine and further progress in research in all these areas. This will create the prerequisites for opening up new areas of pharmacotherapy, obtaining more physiological, harmless drugs both with the help of chemical or microbiological synthesis, and by isolating biologically active substances from plant or animal raw materials. Priority developments are in the field of obtaining insulin, growth hormones, drugs for the treatment of AIDS, alcoholism, and the production of monoclonal bodies. Active research is being carried out in the field of creating other cardiovascular, anti-inflammatory, diuretic, neuroleptic, anti-allergic drugs, immunomodulators, as well as semi-synthetic antibiotics, cephalosporins and hybrid antibiotics. The most promising is the creation of drugs based on the study of natural peptides, polymers, polysaccharides, hormones, enzymes and other biologically active substances. The identification of new pharmacophores and targeted synthesis of generations of drugs based on previously unexplored aromatic and heterocyclic compounds related to the biological systems of the body are extremely important.

The production of new synthetic drugs is practically limitless, since the number of synthesized compounds increases with their molecular weight. For example, the number of even the simplest carbon-hydrogen compounds with a relative molecular weight of 412 exceeds 4 billion substances.

In recent years, the approach to the process of creating and researching synthetic drugs has changed. From a purely empirical "trial and error" method, researchers are increasingly moving to the use of mathematical methods for planning and processing the results of experiments, the use of modern physical and chemical methods. This approach opens up wide opportunities for predicting the likely types of biological activity of synthesized substances, reducing the time for creating new drugs. In the future, the creation and accumulation of data banks for computers, as well as the use of computers to establish the relationship between the chemical structure and the pharmacological action of synthesized substances, will become increasingly important. Ultimately, these works should lead to the creation of a general theory of the directed design of effective drugs related to the systems of the human body.

The creation of new drugs of plant and animal origin consists of such main factors as the search for new species of higher plants, the study of organs and tissues of animals or other organisms, and the establishment of the biological activity of the chemicals they contain.

Of no small importance are also the study of new sources of obtaining drugs, the widespread use for their production of waste from chemical, food, woodworking and other industries. This direction is directly related to the economics of the chemical and pharmaceutical industry and will help reduce the cost of drugs. Especially promising is the use of modern methods of biotechnology and genetic engineering for the creation of drugs, which are increasingly being used in the chemical and pharmaceutical industry.

Thus, the modern nomenclature of drugs in various pharmacotherapeutic groups requires further expansion. Created new drugs are promising only if they surpass existing ones in terms of their effectiveness and safety, and meet world requirements in terms of quality. In solving this problem, an important role belongs to specialists in the field of pharmaceutical chemistry, which reflects the social and medical significance of this science. The most widely involving chemists, biotechnologists, pharmacologists and clinicians, comprehensive research in the field of creating new highly effective drugs is carried out within the framework of subprogram 071 "Creation of new drugs by methods of chemical and biological synthesis."

Along with the traditional work on the screening of biologically active substances, the need to continue which is obvious, studies on the directed synthesis of new drugs are gaining more and more weight. Such works are based on the study of the mechanism of pharmacokinetics and drug metabolism; revealing the role of endogenous compounds in biochemical processes that determine one or another type of physiological activity; study of possible ways of inhibition or activation of enzyme systems. The most important basis for the creation of new drugs is the modification of the molecules of known drugs or natural biologically active substances, as well as endogenous compounds, taking into account their structural features and, in particular, the introduction of "pharmacophore" groups, the development of prodrugs. When developing drugs, it is necessary to achieve an increase in bioavailability and selectivity, regulation of the duration of action by creating transport systems in the body. For targeted synthesis, it is necessary to identify the correlation between the chemical structure, physicochemical properties, and biological activity of compounds, using computer technology to design drugs.

In recent years, the structure of diseases and the epidemiological situation have changed significantly, in highly developed countries the average life expectancy of the population has increased, and the incidence rate among the elderly has increased. These factors have determined new directions in the search for drugs. There was a need to expand the range of drugs for the treatment of various types of neuropsychiatric diseases (parkinsonism, depression, sleep disorders), cardiovascular diseases (atherosclerosis, arterial hypertension, ischemic heart disease, heart rhythm disturbances), diseases of the musculoskeletal system (arthritis, spinal diseases), lung diseases (bronchitis, bronchial asthma). Effective drugs for the treatment of these diseases can significantly affect the quality of life and significantly prolong the active period of people's lives, incl. old age. Moreover, the main approach in this direction is the search for mild drugs that do not cause drastic changes in the basic functions of the body, showing a therapeutic effect due to the influence on the metabolic links of the pathogenesis of the disease.

The main areas of search for new and modernization of existing vital drugs are:

* synthesis of bioregulators and metabolites of energy and plastic metabolism;

* identification of potential drugs during the screening of new products of chemical synthesis;

* synthesis of compounds with programmable properties (modification of the structure in the known series of drugs, resynthesis of natural phytosubstances, computer search for biologically active substances);

* stereoselective synthesis of eutomers and the most active conformations of socially significant drugs.

Development of methods for pharmaceutical and biopharmaceutical analysis. The solution of this important problem is possible only on the basis of fundamental theoretical studies of the physical and chemical properties of drugs with the wide use of modern chemical and physicochemical methods. The use of these methods should cover the entire process from the creation of new drugs to the quality control of the final product of production. It is also necessary to develop new and improved regulatory documentation for drugs and drug products, reflecting the requirements for their quality and ensuring standardization.

On the basis of scientific analysis by the method of expert assessments, the most promising areas of research in the field of pharmaceutical analysis were identified. An important place in these studies will be occupied by work on improving the accuracy of the analysis, its specificity and sensitivity, the desire to analyze very small amounts of drugs, including in a single dose, and also to perform the analysis automatically and in a short time. Undoubted importance is the reduction in labor intensity and the increase in the efficiency of analysis methods. It is promising to develop unified methods for the analysis of drug groups united by the relationship of the chemical structure based on the use of physicochemical methods. Unification creates great opportunities for increasing the productivity of the analytical chemist.

In the coming years, chemical titrimetric methods will retain their importance, having a number of positive aspects, in particular, high accuracy of determinations. It is also necessary to introduce into pharmaceutical analysis such new titrimetric methods as buretless and indicatorless titration, dielectrometric, biamperometric and other types of titration in combination with potentiometry, including in two-phase and three-phase systems.

In recent years, fiber optic sensors (without indicators, fluorescent, chemiluminescent, biosensors) have been used in chemical analysis. They make it possible to remotely study processes, allow determining the concentration without disturbing the state of the sample, and their cost is relatively low. Further development in pharmaceutical analysis will be kinetic methods, which are highly sensitive both in testing purity and quantification.

The laboriousness and low accuracy of biological test methods make it necessary to replace them with faster and more sensitive physicochemical methods. The study of the adequacy of biological and physicochemical methods for the analysis of drugs containing enzymes, proteins, amino acids, hormones, glycosides, antibiotics is a necessary way to improve pharmaceutical analysis. In the next 20-30 years, the leading role will be occupied by optical, electrochemical, and especially modern chromatographic methods, as they most fully meet the requirements of pharmaceutical analysis. Various modifications of these methods will be developed, for example, difference spectroscopy of the type of differential and derivative spectrophotometry. In the field of chromatography, along with gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC) is gaining more and more priority.

The quality of the resulting drugs depends on the degree of purity of the initial products, compliance with the technological regime, etc. Therefore, an important area of ​​research in the field of pharmaceutical analysis is the development of methods for quality control of the initial and intermediate products of drug production (step-by-step production control). This direction follows from the requirements that the OMP rules impose on the production of drugs. Automated methods of analysis will be developed in factory control and analytical laboratories. Significant opportunities in this regard are opened by the use of automated flow-injection systems for step-by-step control, as well as GLC and HPLC for serial control of FPP. A new step has been taken towards the full automation of all analysis operations, which is based on the use of laboratory robots. Robotics has already found wide use in foreign laboratories, especially for sampling and other auxiliary operations.

Further improvement will require methods for analyzing ready-made, including multicomponent, LF, including aerosols, eye films, multilayer tablets, and spansules. To this end, hybrid methods based on a combination of chromatography with optical, electrochemical and other methods will be widely used. The express analysis of individually manufactured dosage forms will not lose its significance, however, here chemical methods will increasingly be replaced by physicochemical ones. The introduction of simple and sufficiently accurate methods of refractometric, interferometric, polarimetric, luminescent, photocolorimetric analysis and other methods makes it possible to increase the objectivity and speed up the assessment of the quality of medicinal products manufactured in pharmacies. The development of such methods is of great relevance in connection with the problem of combating the falsification of drugs that has arisen in recent years. Along with legislative and legal norms, it is absolutely necessary to strengthen control over the quality of drugs of domestic and foreign production, incl. express methods.

An extremely important area is the use of various methods of pharmaceutical analysis to study the chemical processes that occur during storage of drugs. The knowledge of these processes makes it possible to solve such urgent problems as the stabilization of drugs and drugs, the development of scientifically based storage conditions for drugs. The practical expediency of such studies is confirmed by their economic significance.

The task of biopharmaceutical analysis includes the development of methods for determining not only drugs, but also their metabolites in biological fluids and body tissues. To solve the problems of biopharmacy and pharmacokinetics, precise and sensitive physicochemical methods for the analysis of drugs in biological tissues and fluids are needed. The development of such methods is among the tasks of specialists working in the field of pharmaceutical and toxicological analysis.

Further development of pharmaceutical and biopharmaceutical analysis is closely related to the use of mathematical methods to optimize drug quality control methods. Information theory is already used in various fields of pharmacy, as well as such mathematical methods as simplex optimization, linear, nonlinear, numerical programming, multifactorial experiment, pattern recognition theory, and various expert systems.

Mathematical methods of experiment planning make it possible to formalize the procedure for studying a particular system and, as a result, obtain its mathematical model in the form of a regression equation that includes all the most significant factors. As a result, optimization of the entire process is achieved and the most probable mechanism of its functioning is established.

Increasingly, modern methods of analysis are combined with the use of electronic computers. This led to the emergence at the intersection of analytical chemistry and mathematics of a new science - chemometrics. It is based on the wide use of methods of mathematical statistics and information theory, the use of computers and computers at various stages of choosing an analysis method, its optimization, processing and interpretation of results.

A very revealing characteristic of the state of research in the field of pharmaceutical analysis is the relative frequency of application of various methods. As of 2000, there has been a downward trend in the use of chemical methods (7.7% including thermochemistry). The same percentage of the use of IR spectroscopy and UV spectrophotometry methods. The largest number of studies (54%) were performed using chromatographic methods, especially HPLC (33%). Other methods account for 23% of the work performed. Therefore, there is a steady trend towards expanding the use of chromatographic (especially HPLC) and absorption methods to improve and unify methods for the analysis of drugs.

2. History of development of pharmaceutical chemistry

2.1 The main stages in the development of pharmacy

The creation and development of pharmaceutical chemistry are closely related to the history of pharmacy. Pharmacy originated in ancient times and had a huge impact on the formation of medicine, chemistry and other sciences.

The history of pharmacy is an independent discipline, which is studied separately. In order to understand how and why pharmaceutical chemistry was born in the bowels of pharmacy, how the process of its formation into an independent science took place, we will briefly consider the individual stages in the development of pharmacy starting from the period of iatrochemistry.

The period of iatrochemistry (XVI - XVII centuries). During the Renaissance, alchemy was replaced by iatrochemistry (medical chemistry). Its founder Paracelsus (1493 - 1541) believed that "chemistry should serve not the extraction of gold, but the protection of health." The essence of the teachings of Paracelsus was based on the fact that the human body is a collection of chemicals and the lack of any of them can cause disease. Therefore, for healing, Paracelsus used chemical compounds of various metals (mercury, lead, copper, iron, antimony, arsenic, etc.), as well as herbal medicines.

Paracelsus conducted a study of the effect on the body of many substances of mineral and plant origin. He improved a number of instruments and apparatus for performing analysis. That is why Paracelsus is rightly considered one of the founders of pharmaceutical analysis, and iatrochemistry - the period of the birth of pharmaceutical chemistry.

Pharmacies in the XVI - XVII centuries. were original centers for the study of chemicals. Substances of mineral, plant and animal origin were obtained and studied in them. A number of new compounds were discovered here, the properties and transformations of various metals were studied. This made it possible to accumulate valuable chemical knowledge and improve the chemical experiment. For 100 years of development of iatrochemistry, science has been enriched with a greater number of facts than alchemy for 1000 years.

The period of the birth of the first chemical theories (XVII - XIX centuries). For the development of industrial production during this period, it was necessary to expand the scope of chemical research beyond the limits of atrochemistry. This led to the creation of the first chemical industries and to the formation of chemical science.

Second half of the 17th century - the period of the birth of the first chemical theory - the theory of phlogiston. With its help, they tried to prove that the processes of combustion and oxidation are accompanied by the release of a special substance - "phlogiston". The theory of phlogiston was created by I. Becher (1635-1682) and G. Stahl (1660-1734). Despite some erroneous assumptions, it was undoubtedly progressive and contributed to the development of chemical science.

In the struggle against the supporters of the phlogiston theory, the oxygen theory arose, which was a powerful impetus in the development of chemical thought. Our great compatriot M.V. Lomonosov (1711 - 1765), one of the first scientists in the world, proved the inconsistency of the phlogiston theory. Despite the fact that oxygen was not yet known, M.V. Lomonosov experimentally showed in 1756 that in the process of combustion and oxidation, it is not decomposition that occurs, but the addition of air "particles" to the substance. Similar results were obtained 18 years later in 1774 by the French scientist A. Lavoisier.

Oxygen was first isolated by the Swedish scientist, pharmacist K. Scheele (1742 - 1786), whose merit was also the discovery of chlorine, glycerin, a number of organic acids and other substances.

Second half of the 18th century was a period of rapid development of chemistry. A great contribution to the progress of chemical science was made by pharmacists, who made a number of remarkable discoveries that are important for both pharmacy and chemistry. So, the French pharmacist L. Vauquelin (1763 - 1829) discovered new elements - chromium, beryllium. Pharmacist B. Courtois (1777 - 1836) discovered iodine in seaweed. In 1807, the French pharmacist Seguin isolated morphine from opium, and his compatriots Pelletier and Caventu were the first to obtain strychnine, brucine, and other alkaloids from plant materials.

The pharmacist Mor (1806 - 1879) did a lot for the development of pharmaceutical analysis. He first used burettes, pipettes, pharmacy scales, which bear his name.

Thus, pharmaceutical chemistry, which originated in the period of iatrochemistry in the 16th century, received its further development in the 17th-18th centuries.

2.2 Development of pharmaceutical chemistry in Russia

The origins of Russian pharmacy. The emergence of pharmacy in Russia is associated with the widespread development of traditional medicine and quackery. Handwritten "healers" and "herbalists" have survived to this day. They contain information about numerous medicines of the plant and animal world. Green shops (XIII - XV centuries) were the first cells of the pharmacy business in Russia. The emergence of pharmaceutical analysis should be attributed to the same period, since there was a need to check the quality of drugs. Russian pharmacies in the XVI - XVII centuries. were a kind of laboratories for the manufacture of not only medicines, but also acids (sulfuric and nitric), alum, vitriol, sulfur purification, etc. Hence, pharmacies were the birthplace of pharmaceutical chemistry.

The ideas of alchemists were alien to Russia, here a genuine craft of making medicines immediately began to develop. Alchemists were involved in the preparation and quality control of medicines in pharmacies (the term "alchemist" has nothing to do with alchemy).

The training of pharmacists was carried out by the first medical school opened in Moscow in 1706. One of the special disciplines in it was pharmaceutical chemistry. Many Russian chemists were educated at this school.

The true development of chemical and pharmaceutical science in Russia is associated with the name of M.V. Lomonosov. On the initiative of M.V. Lomonosov, in 1748 the first scientific chemical laboratory was created, and in 1755 the first Russian university was opened. Together with the Academy of Sciences, these were centers of Russian science, including chemical and pharmaceutical sciences. M.V. Lomonosov owns wonderful words about the relationship between chemistry and medicine: "... A physician cannot be perfect without a satisfied knowledge of chemistry, and all the shortcomings, all the excesses and from them encroachments occurring in medical science; additions, aversions and corrections from one almost chemistry should hope."

One of the many successors of M.V. Lomonosov was an apothecary student, and then a prominent Russian scientist T.E. Lovits (1757 - 1804). He was the first to discover the adsorption capacity of coal and used it to purify water, alcohol, and tartaric acid; developed methods for obtaining absolute alcohol, acetic acid, grape sugar. Among the numerous works of T.E. Lovits, the development of a microcrystalloscopic method of analysis (1798) is directly related to pharmaceutical chemistry.

A worthy successor to M.V. Lomonosov was the greatest Russian chemist V.M. Severgin (1765-1826). Among his many works, two books published in 1800 are of the greatest importance for pharmacy: "A Method for Testing the Purity and Integrity of Chemical Products of Medicinal Products" and "A Method for Testing Mineral Waters". Both books are the first domestic manuals in the field of research and analysis of medicinal substances. Continuing the thought of M.V. Lomonosov, V.M. Severgin emphasizes the importance of chemistry in assessing the quality of drugs: "Without knowledge in chemistry, drug testing cannot be undertaken." The author deeply scientifically selects only the most accurate and accessible methods of analysis for the study of drugs. The order and plan for the study of medicinal substances proposed by V.M. Severgin has changed little and is now used in the preparation of the State Pharmacopoeia. V.M. Severgin created the scientific basis not only for pharmaceutical, but also for chemical analysis in our country.

The works of the Russian scientist A.P. Nelyubin (1785 - 1858) are rightly called the "Encyclopedia of Pharmaceutical Knowledge". He first formulated the scientific foundations of pharmacy, carried out a number of applied research in the field of pharmaceutical chemistry; improved methods for obtaining salts of quinine, created devices for obtaining ether and for testing arsenic. A.P. Nelyubin conducted extensive chemical studies of Caucasian mineral waters.

Until the 40s of the XIX century. in Russia there were many chemists who made a great contribution to the development of pharmaceutical chemistry with their work. However, they worked separately, there were almost no chemical laboratories, there was no equipment and scientific chemical schools.

The first chemical schools and the creation of new chemical theories in Russia. The first Russian schools of chemistry, founded by A.A. Voskresensky (1809-1880) and N.N. Zinin (1812-1880), played an important role in the training of personnel, in the creation of laboratories, had a great including pharmaceutical chemistry. A.A. Voskresensky carried out with his students a number of studies directly related to pharmacy. They isolated the alkaloid theobromine, and studied the chemical structure of quinine. The outstanding discovery of N.N. Zinin was the classical reaction of the transformation of aromatic nitro compounds into amino compounds.

D.I.Mendeleev wrote that A.A.Voskresensky and N.N.Zinin are "the founders of the independent development of chemical knowledge in Russia". World fame was brought to Russia by their worthy successors D.I. Mendeleev and A.M. Butlerov.

DI Mendeleev (1834 - 1907) is the creator of the Periodic Law and the Periodic Table of Elements. The great importance of the Periodic Law for all chemical sciences is well known, but it also contains a deep philosophical meaning, since it shows that all elements form a single system connected by a common pattern. In his multifaceted scientific activity, D.I. Mendeleev paid attention to pharmacy. Back in 1892, he wrote about the need to "set up factories and laboratories in Russia for the production of pharmaceutical and hygienic preparations" in order to free them from imports.

The works of A.M. Butlerov also contributed to the development of pharmaceutical chemistry. A.M. Butlerov (1828 - 1886) received urotropin in 1859; studying the structure of quinine, discovered quinoline. He synthesized sugary substances from formaldehyde. However, world fame brought him the creation (1861) of the theory of the structure of organic compounds.

The periodic system of elements by D.I. Mendeleev and the theory of the structure of organic compounds by A.M. Butlerov had a decisive influence on the development of chemical science and its connection with production.

Research in the field of chemotherapy and chemistry of natural substances. At the end of the 19th century, new studies of natural substances were carried out in Russia. As early as 1880, long before the works of the Polish scientist Funk, the Russian physician N.I. Lunin suggested that in addition to protein, fat, and sugar, food contained "substances indispensable for nutrition." He experimentally proved the existence of these substances, which were later called vitamins.

In 1890, the book by E. Shatsky "Teaching about plant alkaloids, glucosides and ptomains" was published in Kazan. It deals with the alkaloids known at that time in accordance with their classification according to the producing plants. Methods for the extraction of alkaloids from plant materials are described, including the apparatus proposed by E. Shatsky.

In 1897, K. Ryabinin's monograph "Alkaloids (Chemical and Physiological Essays)" was published in St. Petersburg. In the introduction, the author points out the urgent need "to have in Russian such an essay on alkaloids, which, with a small volume, would give an accurate, essential and comprehensive concept of their properties." The monograph has a short introduction describing general information about the chemical properties of alkaloids, as well as sections that give summary formulas, physical and chemical properties, reagents used for identification, and information on the use of 28 alkaloids.

Chemotherapy originated at the turn of the 20th century. due to the rapid development of medicine, biology and chemistry. Both domestic and foreign scientists have contributed to its development. One of the creators of chemotherapy is the Russian doctor D.JI. Romanovsky. In 1891, he formulated and experimentally confirmed the foundations of this science, pointing out that it is necessary to look for a "substance" that, when introduced into a diseased organism, will cause the least harm to the latter and cause the greatest destructive effect in the pathogenic agent. This definition has retained its meaning to this day.

Extensive research in the field of the use of dyes and organoelement compounds as medicinal substances was carried out by the German scientist P. Ehrlich (1854 - 1915) at the end of the 19th century. He was the first to propose the term "chemotherapy". Based on the theory developed by P. Ehrlich, called the principle of chemical variation, many scientists, including Russians (O.Yu. Magidson, M.Ya. Kraft, M.V. Rubtsov, A.M. Grigorovsky), created a large number of chemotherapeutic drugs with antimalarial activity.

The creation of sulfanilamide drugs, which marked the beginning of a new era in the development of chemotherapy, is associated with the study of the azo dye prontosil, discovered in search of drugs for the treatment of bacterial infections (G. Domagk). The discovery of prontosil was a confirmation of the continuity of scientific research - from dyes to sulfonamides.

Modern chemotherapy has a huge arsenal of drugs, among which the most important place is occupied by antibiotics. First discovered in 1928 by the Englishman A. Fleming, the antibiotic penicillin was the ancestor of new chemotherapeutic agents effective against pathogens of many diseases. The works of A. Fleming were preceded by research by Russian scientists. In 1872, V.A. Manassein established the absence of bacteria in the culture liquid when growing green mold (Pénicillium glaucum). A.G. Polotebnov experimentally proved that the cleansing of pus and wound healing occur faster if a mold is applied to it. The antibiotic effect of mold was confirmed in 1904 by veterinarian M.G. Tartakovsky in experiments with the causative agent of chicken plague.

The research and production of antibiotics has led to the creation of a whole branch of science and industry, revolutionized the field of drug therapy for many diseases.

Thus, conducted by Russian scientists at the end of the XIX century. research in the field of chemotherapy and chemistry of natural substances laid the foundation for obtaining new effective drugs in subsequent years.

2.3 Development of pharmaceutical chemistry in the USSR

The formation and development of pharmaceutical chemistry in the USSR took place in the early years of Soviet power in close connection with chemical science and production. The domestic schools of chemists created in Russia, which had a huge impact on the development of pharmaceutical chemistry, have been preserved. Suffice it to mention the major schools of organic chemists A.E. Favorsky and N.D. Zelinsky, researcher of the chemistry of terpenes S.S. geochemistry, N.S. Kurnakova - in the field of physical and chemical research methods. The center of science in the country is the Academy of Sciences of the USSR (now - NAS).

Like other applied sciences, pharmaceutical chemistry can develop only on the basis of fundamental theoretical research that was conducted at the research institutes of chemical and biomedical profile of the USSR Academy of Sciences (NAS) and the USSR Academy of Medical Sciences (now AMN). Scientists of academic institutions are directly involved in the creation of new drugs.

Back in the 30s, the first research in the field of chemistry of natural biologically active substances was carried out in the laboratories of A.E. Chichibabin. These studies were further developed in the works of I. L. Knunyants. He, together with O.Yu. Magidson, was the creator of the technology for the production of the domestic antimalarial drug akrikhin, which made it possible to free our country from importing antimalarial drugs.

An important contribution to the development of the chemistry of drugs with a heterocyclic structure was made by N.A. Preobrazhensky. Together with his colleagues, he developed and introduced into production new methods for obtaining vitamins A, E, PP, synthesized pilocarpine, studied coenzymes, lipids and other natural substances.

V.M. Rodionov had a great influence on the development of research in the field of chemistry of heterocyclic compounds and amino acids. He was one of the founders of the domestic industry of fine organic synthesis and chemical-pharmaceutical industry.

A very great influence on the development of pharmaceutical chemistry was exerted by the studies of the school of A.P. Orekhov in the field of alkaloid chemistry. Under his leadership, methods were developed for the isolation, purification and determination of the chemical structure of many alkaloids, which then found application as medicines.

On the initiative of M.M. Shemyakin, the Institute of Chemistry of Natural Compounds was established. Here fundamental research is being carried out in the field of chemistry of antibiotics, peptides, proteins, nucleotides, lipids, enzymes, carbohydrates, steroid hormones. On this basis, new drugs have been created. The Institute laid the theoretical foundations of a new science - bioorganic chemistry.

The studies carried out by GV Samsonov at the Institute of Macromolecular Compounds made a great contribution to solving the problems of purification of biologically active compounds from accompanying substances.

Close ties connect the Institute of Organic Chemistry with research in the field of pharmaceutical chemistry. During the Great Patriotic War, such preparations as Shostakovsky's balm, phenamine, and later promedol, polyvinylpyrrolidone, etc. were created here. formed the basis of new ways of obtaining vitamin Be and its analogues. Work has been carried out in the field of the synthesis of anti-tuberculosis antibiotics and the study of the mechanism of their action.

Research in the field of organoelement compounds carried out in the laboratories of A.N. Nesmeyanov, A.E. Arbuzov and B.A. Arbuzov, M.I. Kabachnik, I.L. These studies were the theoretical basis for the creation of new drugs, which are organoelement compounds of fluorine, phosphorus, iron and other elements.

At the Institute of Chemical Physics, N.M. Emanuel was the first to express the idea of ​​the role of free radicals in suppressing the function of a tumor cell. This allowed the creation of new anticancer drugs.

The development of pharmaceutical chemistry was also greatly facilitated by the achievements of the domestic medical and biological sciences. The work of the school of the great Russian physiologist I.P. Pavlov, the work of A.N. Bach and A.V. Palladin in the field of biological chemistry, etc. had a huge impact.

at the Institute of Biochemistry. A.N.Bakh, under the leadership of V.N.Bukin, developed methods for the industrial microbiological synthesis of vitamins B12, B15, etc.

Fundamental research in the field of chemistry and biology carried out at the institutes of the National Academy of Sciences creates a theoretical basis for the development of targeted synthesis of medicinal substances. Especially important are studies in the field of molecular biology, which gives a chemical interpretation of the mechanism of biological processes occurring in the body, including under the influence of medicinal substances.

A great contribution to the creation of new drugs is made by research institutes of the Academy of Medical Sciences. Extensive synthetic and pharmacological research is carried out by the institutes of the National Academy of Sciences together with the Institute of Pharmacology of the Academy of Medical Sciences. Such a commonwealth made it possible to develop the theoretical foundations for the targeted synthesis of a number of drugs. Synthetic chemists (N.V. Khromov-Borisov, N.K. Kochetkov), microbiologists (Z.V. Ermolyeva, G.F. Gause and others), pharmacologists (S.V. Anichkov, V.V. Zakusov, M.D. Mashkovsky, G.N. Pershin and others) created original medicinal substances.

On the basis of fundamental research in the field of chemical and biomedical sciences, pharmaceutical chemistry developed in our country and became an independent branch. Already in the first years of Soviet power, pharmaceutical research institutes were created.

In 1920, the Scientific Research Chemical and Pharmaceutical Institute was opened in Moscow, which in 1937 was renamed VNIHFI named after V.I. S. Ordzhonikidze. Somewhat later, such institutes (NIHFI) were established in Kharkov (1920), Tbilisi (1932), Leningrad (1930) (in 1951 LenNIKhFI was merged with the chemical-pharmaceutical educational institute). In the postwar years, NIHFI was formed in Novokuznetsk.

VNIHFI is one of the largest research centers in the field of new drugs. The scientists of this institute solved the iodine problem in our country (O.Yu. Magidson, A.G. Baichikov and others), developed methods for obtaining antimalarial drugs, sulfonamides (O.Yu. Magidson, M.V. Rubtsov and others. ), anti-tuberculosis drugs (S.I. Sergievskaya), organoarsenic drugs (G.A. Kirchhoff, M.Ya. Kraft, etc.), steroid hormonal drugs (V.I. Maksimov, N.N. Suvorov, etc.) , major research in the field of chemistry of alkaloids was carried out (A.P. Orekhov). Now this institute is called the "Center for the Chemistry of Medicinal Products" - VNIKhFI im. S. Ordzhonikidze. Scientific personnel are concentrated here, coordinating activities for the creation and implementation of new medicinal substances into the practice of chemical and pharmaceutical enterprises.

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Year of issue: 2004

Genre: Pharmacology

Format: DjVu

Quality: Scanned pages

Description: The volume of the material presented in the textbook "Pharmaceutical Chemistry" significantly exceeds the content of the curriculum for pharmaceutical schools. The authors deliberately went for such an extension, taking into account the examples of some foreign and domestic textbooks, where the subject is presented with the involvement of information about the latest scientific achievements. This allows the teacher to independently select the material recommended by the program in accordance with the established traditions of the educational institution. Taking into account the high level of preparation of some students, a broader presentation of the subject will help them in studying some sections.
A feature of the presentation of the material is the use of data from the Russian Encyclopedia of Medicines (2003), the US Pharmacopoeia (USP-24), the European Pharmacopoeia (EF-2002), the British Pharmacopoeia (BF-2001), scientific publications of recent years and current scientific periodicals on the chemistry of drugs (LS). The use of foreign pharmacopeias in the preparation of the textbook is quite justified, since the domestic Pharmacopoeia has not been republished in full since 1968, and the receipt of temporary pharmacopoeial articles by educational institutions is associated with significant material costs. In addition, in Russia, as is known, work is underway to introduce GP (Good Practice - Good Practice) methods into pharmacy at all stages of the drug's "life". Good Pharmaceutical Practice has crossed the borders of the US and Europe. Therefore, the future domestic Pharmacopoeia will certainly absorb a lot of positive things that have been achieved and used in countries that are members of the European Pharmacopoeia (EP) community as members and observers.
It is quite possible that the integration of countries at all levels will facilitate the task of Russia joining the European Pharmacopoeia, as 27 states have already done. Such unity, coordination (harmonization) of the pharmacopoeia of different countries is not accidental: the medicine that we sell or purchase has ceased to belong to one country. Substances, excipients, reagents, packaging, quality control methods for all components, analysis equipment are the fruit of the work of specialists from different countries. Ultimately, drugs may end up on the market of a completely different state. Unfortunately, at present, the requirements used in different countries to assess the safety and effectiveness of drugs differ. That is why the issue of harmonizing the Pharmacopoeia of various states, both producing drugs and using them on their territory, is so important.
Approaches unconventional for pharmaceutical chemistry have been used to characterize the biological activity of drugs in biological media. Thus, the authors applied the methods of "pH-diagrams" and "pH-potential" diagrams for acid-base and redox processes involving drugs. When describing the features of synthesis, analysis, storage conditions, therapeutic activity, fundamental laws were used, in particular, the law of mass action for equilibrium and the law of mass action for speed.
For the first time in the educational literature for assessing the pyrogenicity of injectable dosage forms, the LAL test is described, which is included in the latest pharmacopoeial editions and meets the requirements of GMP (Good Manufacturing Practice - Good Manufacturing Practice).
Unfortunately, some issues important for pharmaceutical chemistry were left out of the exposition, which is explained by the limitations of the volume of the publication.
The textbook "Pharmaceutical Chemistry" was written by a team of authors representing three interrelated areas - biology, chemistry, and pharmacy.
Glushchenko Natalia Nikolaevna - Doctor of Biological Sciences, Head. Laboratory of Problems of the Impact of Heavy Metals on Biosystems of the Institute of Energy Problems of Chemical Physics of the Russian Academy of Sciences.
Pleteneva Tatyana Vadimovna - Professor, Doctor of Chemistry, Head of the Department of Pharmaceutical and Toxicological Chemistry, Faculty of Medicine, Peoples' Friendship University of Russia.
Popkov Vladimir Andreevich - Professor, Doctor of Pharmaceutical Sciences, Doctor of Pedagogical Sciences, Academician of the Academy of Education, Head of the Department of General Chemistry, Moscow Medical Academy. THEM. Sechenov.
The authors will be grateful for critical comments and suggestions for improving the content of the textbook.

The textbook "Pharmaceutical Chemistry" is intended for students of secondary medical schools and colleges studying in the specialty 0405 "Pharmacy". Separate sections of the textbook can be used by university students and students of advanced training faculties.

"Pharmaceutical Chemistry"

INTRODUCTION TO DRUG CHEMISTRY
Pharmaceutical Chemistry Content

1. Relationship of pharmaceutical chemistry with other sciences
2. Basic terms and concepts used in pharmaceutical chemistry
3. Classification of medicines

Obtaining and researching medicines. Basic provisions and documents regulating pharmaceutical analysis

1. Sources of obtaining medicines
2. The main directions of search and creation of medicinal substances
3. Criteria for the quality of medicines
4. Standardization of medicines. Control and Permit System for Quality Assurance of Medicinal Products
5. Methods of drug analysis
6. General information about methods and tests of drugs for toxicity, sterility and microbiological purity
7. Determination of bioequivalence and bioavailability of drugs by kinetic methods
8. Shelf life and stabilization of medicines
9. Intra-pharmacy drug control

CHEMISTRY OF DRUGS OF INORGANIC NATURE
s-element drugs

1. General characteristics of the group
2. Magnesium Drug Chemistry
3. Chemistry of Calcium Drugs
4. Chemistry of barium drugs

Medicines of p-elements

1. Medicines of p-elements of group VII
2. Medicines of p-elements of group VI
3. Medicines of group V
4. Medicines of p-elements of group IV
5. Medicines of p-elements of group III

Medicines of d- and f-elements

1. Drugs of d-elements of group I
2. Drugs of d-elements of group II
3. Drugs of d-elements of group VIII
4. f-element drugs

Radiopharmaceuticals
Homeopathic medicines
CHEMISTRY OF DRUGS OF ORGANIC NATURE
Medicinal products of organic nature and features of their analysis

1. Classification
2. Analysis

Acyclic drugs

1. Alcohols
2. Aldehydes
3. Carbohydrates
4. Ethers
5. carboxylic acids. Aminocarboxylic acids and their derivatives

Carbocyclic drugs

1. Aromatic amino alcohols
2. Phenols, quinones and their derivatives
3. Aromatic acids, hydroxy acids and their derivatives
4. Aromatic amino acids
5. Aromatic acetamine derivatives

Heterocyclic drugs

1. Furan derivatives
2. Pyrazole derivatives
3. Imidazole derivatives
4. Pyridine derivatives
5. Pyrimidine derivatives
6. Tropane derivatives
7. Quinoline derivatives
8. Isoquinoline derivatives
9. Purine derivatives
10. Isoalloxazine derivatives

Antibiotics

1. Antibiotics with an azetidine core (p-lactamides)
2. Tetracycline antibiotics
3. Antibiotics - aminoglycosides
4. Aromatic antibiotics - derivatives of nitrophenylalkylamines (chloramphenicol group)
5. Antibiotics macrolides and azalides

Bibliography