Simultaneous analysis of oral anticancer drugs for renal cell carcinoma in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry

Shinya Takasaki, Masaki Tanaka, Masafumi Kikuchi, Masamitsu Maekawa, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano

研究成果: Article査読

18 被引用数 (Scopus)

抄録

An analytical method using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous measurement of four tyrosine kinase inhibitors used for renal cell carcinoma and their metabolites in human plasma. Despite their similar structures, it is difficult to measure plasma levels of these compounds simultaneously using optimal MS parameters for each compound because a quantitative range exceeding 50,000-fold is required. To overcome this problem, we used a linear range shift technique using in-source collision-induced dissociation. Linearity ranges of sorafenib, sorafenib N-oxide, sunitinib, N-desethyl sunitinib, axitinib and pazopanib were 100–10,000, 10–1,000, 1–100, 1–100, 1–100 and 500–50,000 ng/mL, respectively. The intra- and inter-day precision and accuracy were high, and coefficients of variation and relative error were <10.3% and within ±11.8%, respectively. The matrix effects of all analytes ranged from 87.7 to 114.8%. Extraction recoveries and overall recoveries showed small extraction loss (<15.0%) for all analytes. Moreover, all cancer patient samples used in this study were successfully quantified and fell within the linear range of measurement. Therefore, this novel analytical system using in-source collision-induced dissociation has sufficient performance to measure plasma concentrations of these four tyrosine kinase inhibitors and their metabolites for therapeutic drug monitoring.

本文言語English
論文番号e4184
ジャーナルBiomedical Chromatography
32
6
DOI
出版ステータスPublished - 2018 6

ASJC Scopus subject areas

  • 分析化学
  • 生化学
  • 分子生物学
  • 薬理学
  • 創薬
  • 臨床生化学

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