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

•We established a LC-ESI-MS/MS method to determine simotinib, a novel TKIs.•The method was applied to a pharmacokinetic study in 12 healthy Chinese volunteers.•The clinical pharmacokinetic parameters of simotinib were reported for the first time.

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 × 150 mm, 5 μm). 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 μg L−1 (r2 = 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 Cmax and Tmax for simotinib were 254.79 ± 98.30 μg L−1 and 1.71 ± 0.48 h, respectively. Plasma concentrations declined with a t1/2 of 5.37 ± 2.32 h. AUC0–t and AUC0→∞ values obtained were 1262.59 ± 501.41 μg L−1 h and 1329.95 ± 517.42 μg L−1 h, respectively.