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International Journal of Analytical Chemistry
Volume 2017, Article ID 2341876, 6 pages
https://doi.org/10.1155/2017/2341876
Research Article

Validation of a Liquid Chromatography-Tandem Mass Spectrometric Assay for Quantitative Analysis of Lenvatinib in Human Plasma

1Division of Pharmacy, National Cancer Center Hospital East, Chiba, Japan
2Division of Functional Imaging, National Cancer Center, Chiba, Japan
3Division of Head and Neck Oncology, National Cancer Center Hospital East, Chiba, Japan
4Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Hyogo, Japan

Correspondence should be addressed to Tomoko Ogawa-Morita; pj.og.ccn.tsae@awagoot

Received 28 March 2017; Accepted 16 May 2017; Published 7 June 2017

Academic Editor: Günther K. Bonn

Copyright © 2017 Tomoko Ogawa-Morita et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Toward conducting clinical pharmacokinetic studies of an antineoplastic agent, lenvatinib, we developed a liquid chromatography-tandem mass spectrometric assay for its quantitative analysis in human plasma. Analyte (lenvatinib) and internal standard (IS, propranolol) in the plasma were extracted by using acetonitrile and chromatographically separated by using a XTerra MS C18 column with 0.2 mL/min flow and mobile phase starting with 0.1% formic acid in water, followed by increasing percentage of acetonitrile. Detection was performed by using combined reversed-phase liquid chromatography-tandem mass spectrometry (LC/MS-MS) with positive ion electrospray ionization. MS-MS ion transitions used were 427.602>371.000 for lenvatinib and 260.064>116.005 for IS. This study was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification, recovery, and matrix effect according to the Guideline on Bioanalytical Method Validation in Pharmaceutical Development in Japan. Calibration curve was plotted by using lenvatinib concentrations ranging within 9.6–200 ng/mL, and correlation coefficients () were in excess of 0.997. Intra- and interday accuracy ranged within 95.8–108.3% with mean recoveries of 66.8% for lenvatinib, and precision was <6.7% at all quality control concentration levels. Matrix effect analysis showed extraction efficiency of 15.7% for lenvatinib. Collectively, these findings demonstrate the feasibility of this method to evaluate kinetic disposition of lenvatinib.