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  2. A validated LC-MS/MS method for the quantification of capivasertib in dog plasma: Application to its pharmacokinetics study

A validated LC-MS/MS method for the quantification of capivasertib in dog plasma: Application to its pharmacokinetics study

  • Biomed Chromatogr. 2020 Oct;34(10):e4920. doi: 10.1002/bmc.4920.
Zhe Zhang 1 2 Li Nong 3 Meng-Lei Chen 1 2 Ming-Hui Liu 1 2 Wen-Wu Cheng 1 2
Affiliations

Affiliations

  • 1 Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 3 Cancer Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract

In this study, a simple and reliable liquid chromatography tandem mass spectrometric method was first developed for the determination of capivasertib in dog plasma with ipatasertib as internal standard. The plasma samples were deproteinated using acetonitrile. An Acquity BEH C18 column (1.7 μm, 2.1 × 50 mm) maintained at 40°C was used for chromatographical separation, with water containing 0.1% formic acid and acetonitrile as mobile phase. Multiple reaction monitoring transitions were m/z 429.2 > 135.1 for capivasertib and m/z 458.2 > 387.2 for ipatasertib, respectively. Excellent linearity was achieved in the concentration range of 1-1,000 ng/ml with a correlation coefficient of >0.9981. The lower limit of quantification was 1 ng/ml. The extraction recovery of capivasertib from dog plasma was >85.81% and no significant matrix effect was found. The intra- and inter-day precision was <9.58% and the accuracy ranged from -10.60% to 12.50%. The validated method was further applied to the pharmacokinetic study of capivasertib in dog plasma after single oral (5 mg/kg) and intravenous (1 mg/kg) administrations. The results revealed that capivasertib was rapidly absorbed into plasma with good bioavailability (47.04%) and low clearance.

Keywords

bioavailability; capivasertib; liquid chromatography tandem mass spectrometry; pharmacokinetics.

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