An established LC-MS/MS method and a developed PK model for the study of pharmacokinetic properties of benapenem in infected mice

doi:10.5246/jcps.2019.11.076

Abstract

Abstract:

Benapenem is a new parenteral beta-lactam antibacterial with a broad antibacterial spectrum. In the present study, we developed and validated a simple, rapid and sensitive assay method using D6-benapenem as internal standard (IS) after one-step precipitation with methanol to determine benapenem in the plasma of infected mice. Separation was achieved on a reverse phase C₁₈ column with a mobile phase composed of acetonitrile containing 0.2% formic acid–water (0.2% formic acid) and 10 mmol/L ammonium acetate in gradient elution mode. A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as detector and operated by multiple reaction monitoring (MRM) in the positive ion mode. Calibration curves were linear (r>0.99) between 10 and 2000 ng/mL. The quantitative limit was 10 ng/mL, and the intra- and inter- precisions were <4.85% and <1.47%, respectively. The extraction recovery of benapenem and IS was 97.07%–107.09% and 92.47%–111.59%, respectively. The intra- and inter- accuracies were –9.70%– –11.00%, and the matrix effects of benapenem and IS were 85.68%–92.04% and 83.17%–92.04%, respectively. The method was successfully applied to the preclinical pharmacokinetic (PK) studies of benapenem. We also developed a two-compartment model to characterize the PK profiles of benapenem in infected mice, which could provide a better understanding of the PK properties of benapenem.

Key words: LC-MS/MS, Benapenem, Infected mice, Pharmacokinetics, Modeling

CLC Number:

R917

Supporting:

Xiwei Ji, Zisheng Kang, Yun Li, Xiping Yang, Xifeng Ma, Chongtie Shi, Yuan Lv. An established LC-MS/MS method and a developed PK model for the study of pharmacokinetic properties of benapenem in infected mice[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(11): 802-811.

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