Stability of cefozopran hydrochloride in aqueous solutions

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: [Formula: see text]. 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.

Effect of Oxygen and Water on the Stability of Imipenem and Cilastatin Sodium for Injection

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Detection of the iron complexes with hydrolysis products of cephalexin and cefradine upon high‐performance liquid chromatography/electrospray ionization mass spectrometry analysis

“…Only in a paper by Chen et al was it mentioned that the product of cephalexin hydrolysis was identified by LC/MS . A number of cephalosporins have been subjected to hydrolysis and the products have been analyzed by ESI‐MS . However, the identified products were degradation products and not hydrolysis products.…”

Adsorption Equilibrium, Kinetics, and Thermodynamic Studies of Cefpirome Sulfate by Using Macroporous Resin

“…The strong activity to resist aerobic Gram-negative bacteria and anaerobic bacteria makes it a pharmacokinetic long-acting drug. Due to the side effects of β-lactams caused by the generation of degradation products, it is important to estimate the stability of cephems. − …”