Abstract
INTRODUCTION.
Spironolactone, included in the list of vital and essential medicinal products, is used for chronic heart failure, arterial hypertension, and primary hyperaldosteronism, which imposes stringent quality requirements for its pharmaceutical substance and finished dosage forms. Current pharmacopoeial requirements for spironolactone differ significantly in impurity control, identification, and assay methods, creating regulatory barriers and complicating quality assessment of the products. To address this problem, the authors performed a comparative analysis of pharmacopoeial requirements to identify areas for harmonization.
AIM.
This study aimed at a comparative evaluation of the requirements of foreign pharmacopoeias and the State Pharmacopoeia of the Russian Federation for the quality of the pharmaceutical substance and tablet dosage forms of spironolactone, in order to identify directions for harmonization of national pharmacopoeial monographs.
DISCUSSION.
The objects of analysis were the current monographs of the European Pharmacopoeia (Ph. Eur.), the United States Pharmacopeia (USP), the British Pharmacopoeia (BP), the Indian Pharmacopoeia (IP), the Japanese Pharmacopoeia (JP), the Chinese Pharmacopoeia (ChP), the International Pharmacopoeia (Ph. Int.), the Korean Pharmacopoeia (KP), and the State Pharmacopoeia of the Russian Federation (SP RF). The methodology was based on a comparative analysis of the monographs for key quality attributes: Identification, Assay, Related substances, and Dissolution (for tablets). The comparative analysis showed that the most stringent and detailed requirements for related substances are imposed by Ph. Eur. and USP, where the determination is performed by HPLC. Several other pharmacopoeias (SP RF, IP, ChP) still use less selective methods (UV spectrophotometry, thin-layer chromatography) and general acceptance criteria for impurities, which do not allow full control of the stability and purity of the substance. For finished dosage forms, a high degree of harmonization of the dissolution test conditions was found, while differences remain in acceptance criteria and analytical methods for quantitation. A priority area for the development of national pharmacopoeial monographs is the implementation of chromatographic methods and the harmonization of impurity limits with leading international standards.
CONCLUSIONS.
The identified differences in pharmacopoeial approaches confirm the advisability of revising national standards toward harmonization with the requirements of Ph. Eur. and USP. Incorporation of a highly specific HPLC method and detailed impurity specification into the SP RF pharmacopoeial monographs for spironolactone‑based medicinal products will help ensure the quality and safety of these products.