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Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (11): 802-811.DOI: 10.5246/jcps.2019.11.076

• Original articles • Previous Articles     Next Articles

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

Xiwei Ji1, Zisheng Kang1, Yun Li1, Xiping Yang2, Xifeng Ma2, Chongtie Shi2, Yuan Lv1*   

  1. 1. Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China
    2. XuanZhu Pharma Co., Ltd., Jinan 250101, Shandong, China
  • Received:2019-07-29 Revised:2019-09-13 Online:2019-12-01 Published:2019-10-11
  • Contact: Tel.: +86-10-82802542, E-mail: jxezz@sina.com
  • Supported by:

    National Natural Science Foundation of China (Grant No. 81803614).

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 acidwater (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: 

Supporting: