The physicochemical properties of the new anxiolytic drug afobazole, which belongs to the group of 2-mercaptobenzimidazole derivatives, have been studied with a view to its pharmacopoeial standardization. It is suggested to check afobazole for the presence of impurities by means of TLC and HPLC. Methods for the standardization of afobazole are developed and a project for the pharmacopoeial article of manufacturer for this drug is formulated.As is known, the class of 2-mercaptobenzimidazole derivatives contains substances possessing gastroprotector, adaptogen, cardiotropic, and anxiolytic properties [1]. The new original domestic drug afobazole also belonging to this class and exhibits pronounced anxiolytic action that is not accompanied by side effects typical of tranquilizers of the benzodiazepine series [2]. Afobazole does not produce sedative (calming), hypnotic, and myorelaxant effects. At present, this drug is in the stage of clinical testing as a specific anxiolytic agent.The chemical structure of afobazole corresponds to 5-ethoxy-2-[2-(morpholino)ethylthio]benzimidazole dihydrochloride.The parent substance is synthesized via the alkylation of 5-ethoxybenzimidazole-2-thione with N-(2-chloroethyl)morpholine hydrochloride. The reaction proceeds on boiling in an alkaline aqueous alcohol medium. The reaction product is isolated by extraction with chloroform. The technical product is obtained by adding a hydrogen chloride solution in anhydrous ethanol to the base solution in an organic solvent until obtaining pH 1 -2. Finally, pharmacopoeial afobazole is obtained by recrystallization from ethanol.The present investigation was aimed at determining the physicochemical properties of afobazole, developing analytical procedures for the identification and determination of afobazole, and establishing maximum storage duration and justified parameters of quality of the parent substance I. EXPERIMENTAL PARTAfobazole appears as a crystalline powder of white color, sometimes with a creamy tint, readily soluble in water (1 g per 5 -8 ml), sparingly soluble in ethyl alcohol (1 g per 13 -14 ml), slightly soluble in chloroform (1 g per 275 -280 ml), and practically insoluble in ether (1 g is not dissolved in 100,000 ml).The parent compound was characterized with respect to the drug solution transparency, color, and pH at a concentration of 1%. This solution is virtually colorless (coloration does not exceed 7b grade standard). With respect to transparency, the optical density of 1% afobazole solution does not exceed turbidity standard I. The 1% aqueous afobazole solution has pH within 2.0 -3.0.The afobazole composition and structure are confirmed by elemental analyses and spectroscopic measurements. The IR spectra in the 4000 -400 cm -1 wavenumber range were recorded on a Perkin-Elmer Model 580 spectrophotometer (Sweden) using samples prepared as KBr pellets or nujol mulls. Since it was found that the characteristic absorption bands of afobazole were more clearly pronounced in the spectra of samples palletized with KBr, this me...

Резюме. На основании опыта использования метода жидкостной хроматографии гидрофильных взаимодействий для анализа соединений различной природы исследована возможность применения хроматографической колонки XBridge Amide 150×4,6 мм для разделения эфиров 4-гидроксибензойной кислоты (парабенов). Сравнивались времена удерживания, порядок выхода и разрешение между пиками парабенов и примеси А (4-гидроксибензойная кислота) при использовании подвижных фаз ацетонитрил-фосфатный буфер с содержанием ацетонитрила 7-10 % и подвижных фаз ацетонитрил-вода с содержанием ацетонитрила 96-99 % на указанной колонке. На основании полученных данных установлено, что для разделения гомологов парабенов между собой предпочтительно использование обращенно-фазового варианта хроматографии, а для анализа примеси 4-гидроксибензойной кислоты-хроматографии гидрофильных взаимодействий. При анализе возможных механизмов удерживания соединений на колонке XBridge Amide сделано предположение, что в отличие от аминогрупп амидные группы сорбента не обладают сродством к фенольным гидроксильным группам парабенов в условиях жидкостной хроматографии гидрофильных взаимодействий.

This investigation was aimed at elaborating procedures for the pharmaceutical analysis of the parenteral dosage form of afobazole, a novel domestic drug with anxiolytic and neuroprotective action. The physicochemical properties of afobazole parenteral dosage form have been studied. Methods for the determination of impurities (TLC, HPLC) and identification and assay of the drug (UV spectrophotometry, HPLC) have been developed.