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

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 below 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.

Biomedical chromatography : BMC. 2017 Dec 28 [Epub ahead of print]

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

Department of Pharmaceutical Sciences, Tohoku University Hospital, Japan., Department of Urology, Tohoku University Hospital, Japan.