STUDY OF THE DEGRADATION PROFILES OF RAMIPRIL AND HYDROCHLOROTHIAZIDE AS A STAGE IN THE DEVELOPMENT OF METHOD FOR DETERMINATION IMPURITIES IN THE COMBINED DOSAGE FORM

Abstract

Introduction. It is important for drug manufacturers, to guarantee the quality of the drug product during the shelf life. Therefore, quality control methods should be suitable stability testing.

The aim of the study – to investigate the degradation profile of ramipril and hydrochlorothiazide and establish the possibility of using the developed method for the simultaneous determination of impurities of both components in the combined preparation.

Research Methods. The research used standard samples of ramipril, hydrochlorothiazide and ramipril impurities A, B, C, D (USP RS), class A reagents, 2.5 mg tablets of Ramipril and Ramipril with Hydrochlorothiazide 10 mg/12.5 mg. The samples were analyzed on a liquid chromatograph with an Agilent 1260 diode array detector. An Inertsil ODS-3 column (4.6×150×3 μm) was used; mobile phase A – 0.2 g/l sodium hexanesulfonate solution (pH 2.7); mobile phase B: acetonitrile; mobile phase speed 1.5 ml/min; detection wavelength – 210 nm; column temperature – 45 °C, gradient elution mode.

Results and Discussion. We have previously developed an HPLC method for the determination of ramipril in tablets, which we tested in our studies to study the degradation profiles. Under the influence of stress factors on the placebo drug, no additional peaks were detected. Alkaline hydrolysis has the most significant effect on the degradation of both ramipril and hydrochlorothiazide. Degradation products of hydrochlorothiazide have retention times from 2 to 5 min, ramipril from 10 to 20 min. That is, the developed methodology allows to determine impurities of both active substances.

Conclusions. The developed analytical procedure can provide simultaneous determination of impurities of ramipril and hydrochlorothiazide while stability testing of the combined dosage form.