Simultaneous determination of zidebactam and cefepime in dog plasma by LC–MS/MS and its application to pre‐clinical pharmacokinetic study

Abstract

A precise and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of zidebactam (ZID) and cefepime (FEP) in dog plasma. Ceftazidime was used as an internal standard. Protein precipitation method was used as sample preparation approach. The calibration curve obtained was linear (r ≥ 0.99) over the concentration range 0.156-80 μg/mL for ZID and 0.312-160 μg/mL for FEP. The method was validated as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 3.5 min for each sample made it possible to analyze the maximum number of samples per day. The proposed method was successfully applied for pharmacokinetic study in beagle dogs.

Assessment of the In Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Murine Lung Infection Model

“…strain, and the methods were consistent with those we have previously described (6,8). Drug concentrations in plasma and bronchoalveolar lavage (BAL) fluid were determined using a validated liquid chromatography-tandem mass spectrometry method (9); drug concentrations in ELF were determined following normalization of drug concentrations in BAL fluid to the urea content in BAL fluid and plasma (8). Following administration of zidebactam single doses at 12.5 mg/kg and 37.5 mg/kg of body weight (based on mean body weight of the study population), the ELF-to-plasma penetration ratios were 0.81 and 0.91, respectively, calculated by dividing the ELF 24-h area under the concentration-time curve (AUC 0 -24 ) by the calculated murine plasma unbound (free) drug AUC 0 -24 (fAUC 0 -24 ).…”

Analytical methods for the determination of certain antibiotics used in critically ill patients

“…Patil et al performed LCMS/MS bioanalytical method for the simultaneous quantification of zidebactam and Cefepime in dog plasma. It was achieved on a Luna HILIC 200A, 100 × 2.0 mm, 3 µm with a guard column and the mobile phase composed of a mixture of buffer solution (10 mM ammonium formate in water pH adjusted to 3.5 with formic acid) and acetonitrile (28:72 v/v) [10] .…”

Development and validation of an LC–ESI–QTOF–MS method to measure cefepime in the plasma and peritoneal fluid of rats using microdialysis: Application in a pilot pharmacokinetic study

“…Cefepime (CEF) {[6 R ,7 R , Z ]‐7‐ [2‐(2‐aminothiazol‐4‐yl)‐2‐(methoxymino) acetomide]‐3‐[1‐methyl pyrrolidinium‐1‐yl] methyl}‐8‐oxo‐5‐thia‐1‐aza‐bicyclo [4.2.0] oct‐2‐ene‐2 carboxylate is a fourth‐generation cephalosporin with a broad spectrum of action against Gram‐positive and Gram‐negative bacteria. It is less susceptible to hydrolysis by AmpC β ‐lactamases (cephalosporinases that hydrolyze cephamycins as well as other extended‐spectrum cephalosporins and are poorly inhibited by clavulanic acid) than other cephalosporins (Barshak, 2021; MacDougall, 2020; Patil et al, 2018; Pilmis et al, 2020). It is used empirically in the treatment of severe hospital‐acquired infections (Zhao et al, 2020).…”