P. Zalewski, R. Skibiński, M. Paczkowska
Apr 2, 2016
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Influential Citations
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Journal
Drug Development and Industrial Pharmacy
Abstract
Abstract The influence of pH on the stability of cefozopran hydrochloride (CZH) was investigated in the pH range of 0.44–13.00. Six degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The degradation of CZH as a result of hydrolysis was a pseudo-first-order reaction. As general acid–base hydrolysis of CZH was not occurred in the solutions of hydrochloric acid, sodium hydroxide, acetate, borate and phosphate buffers, kobs = kpH because specific acid–base catalysis was observed. Specific acid–base catalysis of CZH consisted of the following reactions: hydrolysis of CZH catalyzed by hydrogen ions (kH+), hydrolysis of dications (k1H2O), monocations (k2H2O) and zwitter ions (k3H2O) and hydrolysis of zwitter ions (k1OH−) and monoanions (k2OH−) of CZH catalyzed by hydroxide ions. The total rate of the reaction was equal to the sum of partial reactions: . CZH similarly like other fourth generation cephalosporin was most stable at slightly acidic and neutral pH and less stable in alkaline pH. The cleavage of the β-lactam ring resulting from a nucleophilic attack on the carbonyl carbon in the β-lactam moiety is the preferred degradation pathway of β-lactam antibiotics in aqueous solutions.