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A great variety of components in multivitamin preparations containing folic acid, and a variety of test methods and conditions of folic acid determination proposed by manufacturers, require alignment of test procedures for products with similar composition.The aim of the study was to compare the results of experimental verification of folic acid determination procedures which use reversed phase high-performance liquid chromatography (RP HPLC) with isocratic elution mode. Materials and methods: The Agilent 1260 Infinity II LC system with a diode array detector (280 nm), isocratic elution mode, C8- and C18-bonded silica gel chromatographic columns, model mixtures containing folic acid, cyanocobalamin, ferrous sulfate, and potassium iodide, were used in the study.Results: The lowest relative standard deviation of the folic acid peak area (RSD=0.09%), and the lowest asymmetry factor (As=1.04) for folic acid were observed for the model mixture “ferrous sulfate+folic acid+cyanocobalamin” and the following test conditions. Column: 250×4.0 mm, silica gel for chromatography, octylsilyl (C8), endcapped; mobile phase: methanol‒phosphate buffer (12:88), pH 6.6; column temperature: 25ºС. The study demonstrated the feasibility of using these conditions for determination of pteroic acid impurity with simultaneous precipitation of interfering ferrous ions, using ethylenediaminetetraacetic acid solution, pH 9.5, as a solvent.Conclusions: RP HPLC can be recommended as an optimal aligned test procedure for determination of folic acid in combination products. It is recommended to use a solution containing folic and pteroic acids for system suitability testing.

Vitamin A is present in multivitamin products mainly in the form of retinol esters: retinyl acetate, retinyl palmitate, and beta carotene—retinol precursor (dimer) found in plants, which is capable of converting into retinol in liver cells. Retinol is determined in medicinal products primarily by high performance liquid chromatography (HPLC), with preliminary purification and vitamin isolation by liquid-liquid extraction. However, scientific literature also describes other methods of sample preparation and analysis of such compounds. An important issue is differentiation of vitamin A from other fat-soluble vitamins often included as components in multivitamin products. The aim of the study was to analyse and summarise data on current methods used for determination of vitamin A and its derivatives in medicinal products. The authors analysed the range of vitamin A products authorised in the Russian Federation, and the test methods described in their product specification files. The study demonstrated that the test method most often used for determination of retinol esters was HPLC with isocratic elution mode using octadecylsilyl packing in the reverse-phase mode, and, less frequently, aminopropylsilyl packing in the normal phase mode. Determination of beta carotene in medicinal products is most often performed using spectrophotometry.

Experimental validation of methods and procedures featured in draft general pharmacopoeial and pharmacopoeial monographs is an important task for Russian compendial science and practice. These studies provide a basis for adopting state compendial drug quality standards. They enable both manufacturers and quality-control organizations to perform independent quality control of drug substances and medicinal preparations that helps to protect public health.

The current classification of impurities in chemical and mineral drug substances is presented. General approaches to standardization of chemical and mineral drug substances according to the Purity section are given depending on their origin and production technology and considering requirements of international and domestic pharmacopoeial practice

Issues related to regulation of the quality of compounded medicinal preparations by the State Pharmacopoeia of the Russian Federation are considered. Topical questions of the development and implementation of both general clauses and particular monographs related to compounded pharmaceuticals in national pharmacopoeial science and practice are discussed.

Scientific research enabled the formulation of methodological approaches to the standardization of biological, herbal, and homeopathic drugs and their analytical methods included in the Russian Federation State Pharmacopoeia XIIIth Ed. The developed General Pharmacopoeial Articles and Pharmacopoeial Articles are fundamental elements of the standardization of medicines circulated on the Russian Federation pharmaceutical market.

The elixir dosage form according to Russian and foreign pharmacopoeias was analyzed. A list of currently registered Russian and foreign drugs in this dosage form was given. The quality parameters by which drugs in the elixir dosage form must be standardized were listed based on an analysis and generalization of information provided in regulatory documentation of Russian and foreign drug manufacturers.

Standard samples constitute one of the key elements in the medicines standardization system. In pharmacopeia analysis in the Russian Federation and many foreign countries, the use of standard samples is regulated by the corresponding normative documents and pharmacopeia monographs. There are different classifications for standard samples and, depending on purpose, certification programs. Standard samples used in compliance with the requirements of pharmacopeia articles or monographs in international, regional and national pharmacopeias are generally termed pharmacopeia standard samples.

Solutions containing pharmaceuticals of various origins are one of the most popular dosage forms. Pharmaceuticals for parenteral, ophthalmic, internal, and external use, among others, are prepared as solutions. However, a general monograph for the Solutions dosage form has not yet appeared in the Russian State Pharmacopoeia. The principal regulations, including relevant monographs of leading global pharmacopoeias, for the quality requirements of the Solutions dosage form were analyzed and enabled a list of the principal quality parameters of solutions, the techniques and methods for their determination, and the normalized ranges that would be used subsequently to compose a general pharmacopoeial monograph Solutions to be compiled.

Reference standards, including pharmacopoeial reference standards, are widely used for quality assessment of drug substances. Leading global pharmacopoeias contain monographs regulating the requirements for the classification, attestation, and use of reference standards. The drug standardization system in the Russian Federation, which includes drug substances, requires revision for the creation and attestation of national reference standards, including pharmacopoeial ones.