Регуляторные исследования и экспертиза лекарственных средств (Feb 2018)
Substantiation of conditions for determination of related substances in bisoprolol fumarate by HPLC
Abstract
The article summarizes the results of information analysis of bisoprolol fumarate synthesis methods which differ in the number of stages and in raw materials used, and are associated with the major identified impurities A, E and G, according to the European Pharmacopoeia (Ph. Eur.). The authors performed a comparative analysis of the test procedures described in manufacturers’ quality standards, Ph. Eur. and United States Pharmacopoeia (USP) and analyzed the results of comparative experimental studies. It was shown that the implementation of the Ph. Eur. test method for related impurities according to «Bisoprolol fumarate» monograph demonstrated a high resolution between the main peak (of bisoprolol) and those of impurities A, E and G. Whereas the performance of the chromatographic system suitability testing according to the USP monograph failed to produce complete resolution between the peaks of bisoprolol and the impurities. The authors investigated the possibility of using a propranolol hydrochloride reference standard to assess the system resolution. The authors identified the conditions for determination of related substances in bisoprolol fumarate, selected chromatographic columns, proposed chromatographic system suitability criteria, including resolution between the peaks of bisoprolol and propranolol, and established limits for impurities.
