LC–MS/MS assay for the quantification of foretinib in rat plasma and its application to preclinical pharmacokinetic study

Abstract

A simple and sensitive ultra‐high‐performance liquid chromatography tandem mass spectrometric method was developed and validated for the determination of foretinib in rat plasma. The analyte and internal standard were extracted from the bio‐samples with acetonitrile and then separated on an Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) using 0.1% formic acid aqueous and acetonitrile as mobile phase, at a flow rate of 0.4 ml/min. The mass detection was performed in positive selected reaction monitoring mode with precursor‐to‐product transitions at m/z 317.1 > 128.1 for foretinib and m/z 502.2 > 323.1 for internal standard. The assay was demonstrated to be linear in the concentration range of 0.5–1000 ng/ml, with correlation coefficient >0.999. The mean extraction recovery of foretinib from rat plasma was within the range of 84.55–88.09%, while the matrix effect was in the range of 88.56–99.21%. The intra‐ and inter‐day precisions were <12.95% and the accuracy ranged from −7.55 to 8.57%. Foretinib was stable in rat plasma under the tested storage conditions. The validated assay was successfully applied to the pharmacokinetic study of foretinib in the rats. The results revealed that foretinib showed moderate elimination half‐life, low clearance and dose‐independent pharmacokinetic profiles inrats.

Determination of Lekethromycin, a Novel Macrolide Lactone, in Rat Plasma by UPLC-MS/MS and Its Application to a Pharmacokinetic Study

“…We have obtained the granted patent in China (CN 103965273 B) for the chemical synthesis and antibacterial bioactivity of the compound, which is currently in preclinical trials [ 27 ]. Since pharmacokinetic information has an important role in many vital aspects of new drug discovery and development [ 28 , 29 , 30 ], development of a fast and accurate method for the determination and monitoring of lekethromycin in rat plasma is urgently required. To the best of our knowledge, there are no prior publications regarding method establishment and validation for the measurement of lekethromycin in biological samples.…”