LC-ESI-MS/MS determination of simotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor: Application to a pharmacokinetic study

Simotinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor. This study presented a sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method using erlotinib as internal standard for the determination of simotinib in human plasma. The method involved a simple liquid-liquid extraction using diethyl ether. The analytes were separated with isocratic gradient elution on an Agilent TC-C18 column (4.6 x 150 mm, 5 mu m). Mass spectrometric detector equipped with electrospray ionization source was carried out in the mode of multiple reaction monitoring (MRM). The monitored transitions were m/z 501.2 -> 182.1 for simotinib and m/z 394.4 -> 278.1 for erlotinib. The calibration curve of simotinib was established over the range of 2.058-3000 mu g L-1 (r(2) =0.9924). The intra- and inter-day precisions were all less than 10%, and all the biases were not more than 7%. This validated method was then successfully applied to a pharmacokinetic study involving twelve healthy Chinese volunteers. The mean C-max and T-max for simotinib were 254.79 +/- 98.30 mu g L-1 and 1.71 +/- 0.48 h, respectively. Plasma concentrations declined with a t(1/2) of 5.37 +/- 2.32 h. AUC(0-t) and AUC(0-infinity) values obtained were 1262.59 +/- 501.41 mu g L-1 h and 1329.95 +/- 517.42 mu g L-1 h, respectively. (C) 2013 Elsevier B.V. All rights reserved.