Affiliation:
1. Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals Zhejiang University of Technology Hangzhou China
2. Zhejiang Institute for Food and Drug Control, Key Laboratory for Core Technology of Generic Drug Evaluation National Medical Product Administration & Key laboratory of Drug Contacting Materials Quality Control of Zhejiang Province Hangzhou China
Abstract
RationaleCloxacillin and flucloxacillin are prone to degradation and polymerization in humid and hot environments, and their polymers have long been recognized to trigger allergic manifestations. A series of the degradation and polymerized impurities in cloxacillin and flucloxacillin were separated and characterized to ensure safe use of these drugs by the public.MethodsBy studying the chromatographic behavior of the degradation impurities and polymerized impurities in reversed‐phase high‐performance liquid chromatography (RP‐HPLC) gradient elution, the impurities in cloxacillin and flucloxacillin were effectively separated and eluted. RP‐HPLC tandem ion trap/time‐of‐flight mass spectrometry (MS) was applied to characterize the structures of unknown impurities eluted from the RP‐HPLC methods for cloxacillin and flucloxacillin. The mechanisms of formation of the impurities in cloxacillin and flucloxacillin were also investigated.ResultsThe structures of 10 unknown impurities in cloxacillin and 8 unknown impurities in flucloxacillin were elucidated based on the high‐resolution MSn data at positive and negative modes, respectively. Six polymerized impurities were found and characterized, of which three were from the polymerization of cloxacillin and three were from the polymerization of flucloxacillin.ConclusionsThe study on the impurity profiles of cloxacillin and flucloxacillin provided a scientific basis for improving their production processes and quality control.