Determination of BPI15086 and its metabolite in human plasma by ultra-high performance liquid chromatography-MS/MS and its application to a pharmacokinetic study

  • Bioanalysis. 2019 Apr;11(8):773-784. doi: 10.4155/bio-2018-0307.
Shaoyuan Wang  1  2 ,  Xin Zheng  1  2 ,  Yanbao Zhang  1  2 ,  Pei Hu  1  2 ,  Lieming Ding  3 ,  Li Mao  3 ,  Ji Jiang  1  2
Affiliations
  • 1. Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100032, PR China.
  • 2. Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Beijing Municipal Science & Technology Commission, Beijing 100195, PR China.
  • 3. Betta Pharmaceuticals Co., Ltd, Zhejiang 311119, PR China.
PMID: 30994009 DOI: 10.4155/bio-2018-0307
Abstract

Aim: BPI15086 is a potent, irreversible mutant-selective inhibitor of both EGFR (EGFR tyrosine kinase inhibitor) and the T790M resistance mutations tyrosine kinase. A simultaneous quantification method of BPI15086 and its main metabolite in human plasma using LC-MS/MS is documented and fully validated in this study. Methodology & results: Plasma samples were extracted and chromatographed on an Acquity ultra-high performance liquid chromatography BEH C18 column with a gradient elution. Detection was performed on a Sciex 5500 QTRAP® mass spectrometer using positive electrospray ionization. The results indicated that the method had excellent sensitivity and specificity. Conclusion: For the first time a sensitive and robust ultra-high performance liquid chromatography-MS/MS method was established and validated of BPI15086 in human plasma, this method was successfully applied in a first-in-human Phase I clinical trial studying the pharmacokinetics of the BPI15086 tablet in Chinese non-small-cell lung Cancer patients.

Keywords
BPI15086; LC–MS/MS; NSCLC; first-in-human; human plasma; method validation; pharmacokinetics.
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