LC–MS/MS and in silico analysis of pharmaceutical impurities in a combination drug for hypertension

Abstract

AbstractThis study intends to develop an essential simultaneous analysis method for the stability study of the combination drugs hydrochlorothiazide, (S)‐amlodipine besylate, and olmesartan medoxomil and identify degradation products. A stress test of the combination drug was performed under thermal/humidity conditions to identify decomposition products expected to be generated under long‐term storage conditions. Six unidentified degradation products were generated from (S)‐amlodipine besylate and olmesartan medoxomil, except for those identified. Unspecified degradation products were identified by degradation prediction software with LC–MS/MS, and genotoxicity was predicted by toxicity prediction software. In silico toxicity, six degradation products were expected to be nonmutagenic. This study describes the development of an analytical method to predict degradation products and determine whether the degradation products are genotoxic. This process will be helpful in further forced degradation studies to predict the toxicity of potential impurities.