ЩОДО СТАНДАРТИЗАЦІЇ СУБСТАНЦІЇ ГІПЕРТРИЛУ

Abstract

ON THE STANDARDIZATION OF HYPERTRIL SUBSTANCE

Kucherenko L.I.

Zaporozhye State Medical University

SPC «Pharmatron»

Key words: substance, Hypertril, standardization, identification, nonaqueous titration

Introduction. Increase of mortality and disability caused by cardiovascular diseases is the problem not only of health protection institutions, it is the social problem of our society. Efficiency of health care service in Ukraine depends on the presence of highly effective competitive drugs of domestic production. Especially it concerns drugs used for treating of cardiovascular diseases, notably coronary heart disease, arterial hypertension, myocardial infarction and acute heart failure. So the development of drugs for treatment of mentioned diseases is the urgent task of modern medicine and pharmacy. According to the recommendations of The European Society of Cardiology important components of complex therapy of heart failure especially after myocardial infarction are the following drugs: β-adrenoceptor antagonists, ACE inhibitors and diuretics. Thus primary task of pharmacy and medicine is the developing and improvement of new highly effective and safe drugs using of which would lead to the improvement of quality of life and its extension. All about mentioned urge to develop perfectly new antianginal and antihypertensive remedy of original structure which has minimum side effects.

At the Pharmaceutical Chemistry Department of Zaporizhzhia State Medical University in collaboration with the SPC "Pharmatron" new original compound – derivative of 4-amino-1,2,4-triazole (drug Hypertril) was synthesized.

Objective. The aim of this investigation is the development of Hypertril substance standardization methods.

Methods. On the basis of structural formula of Hypertril and methods of its receiving we have worked out the draft of quality control methods (QCM) for the substance. While developing it we used latest modern methods of standardization which are ordered by State Pharmacopoeia of Ukraine (SPU) and the European Pharmacopoeia.

Results and discussion. For identification of Hypertril substance we proposed to carry out characteristic reaction (C) for bromide ion notably with the solution of chloramine in the presence of dilute hydrochloric acid and chloroform (chloroform layer receives yellow-brown colour). Besides, taking into account modern standardization methods we proposed to determine correspondence of infrared spectrum of the substance with the infrared spectrum of pharmacopeia standard sample.

Next task was the development of methods of quantitation of Hypertril substance. First we studied the possibility of Hypertril substance titration with 0.1M solution of perchloric acid with the use of internal indicator and determination of point of equivalence potentiometrically. As solvent we used acetic acid nonaqueous. The investigation showed that the substance is soluble in acetic acid nonaqueous only under prolonged heating. Results received were satisfactory and were from 98.5% up to 101%. But taking into consideration the time one analysis takes we believe this method is not to be practical. To reduce the Hypertril substance analysis duration we proposed to dissolve weighed portion preliminarily in formic acid nonaqueous and then add acetic acid nonaqueous. During the analysis of Hypertril substance according to this method we received unsatisfactory results in the limits from 94% up to 98%. In further investigations we used as solvent the mixture of formic acid nonaqueous with acetic anhydride. As indicator we used crystal violet and defined point of equivalence potentiometrically. While using internal indicator there were some difficulties because the transition of coloring was not clear. Thus we proposed to define point of equivalence potentiometrically. During analysis we received satisfactory results and analysis duration shortened three times.

Conclusions. According to the results of the investigations we can conclude that developed method of defining of quantitative content of Hypertril substance by nonaqueous titration is easy-to-use and simple, accurate, reproducible and corresponds to all demands of State Pharmacopoeia and international standards. Further worked out methods of qualitative and quantitative determination of Hypertril substance are planned to introduce into QCM for Hypertril substance.