title: 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.
authors.affiliation: a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Poznan University of Medical Sciences , Grunwaldzka , Poznań , Poland and.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Zalewski
authors.affiliation: b Department of Medicinal Chemistry , Medical University of Lublin , Jaczewskiego , Lublin , Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Skibiński
authors.affiliation: a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Poznan University of Medical Sciences , Grunwaldzka , Poznań , Poland and.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paczkowska
authors.affiliation: a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Poznan University of Medical Sciences , Grunwaldzka , Poznań , Poland and.
authors.forename: Piotr
authors.initials: P
authors.lastname: Garbacki
authors.affiliation: a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Poznan University of Medical Sciences , Grunwaldzka , Poznań , Poland and.
authors.forename: Alicja
authors.initials: A
authors.lastname: Talaczyńska
authors.affiliation: a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Poznan University of Medical Sciences , Grunwaldzka , Poznań , Poland and.
authors.forename: Judyta
authors.initials: J
authors.lastname: Cielecka-Piontek
authors.affiliation: a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Poznan University of Medical Sciences , Grunwaldzka , Poznań , Poland and.
authors.forename: Anna
authors.initials: A
authors.lastname: Jelińska
mesh_terms: D002511:Cephalosporins / Q000737:chemistry* / Q000378:metabolism*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D019999:Pharmaceutical Solutions / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry* / Q000378:metabolism*; D000097586:Cefozopran
chemical_list: D002511:Cephalosporins; D019999:Pharmaceutical Solutions; D014867:Water; D000097586:Cefozopran
keywords: Cefozopran hydrochloride; HPLC; Q-TOF; degradation products; stability in aqueous solutions