Development of a validated LC-MS/MS method for quantification of phosphoinositide 3 kinase inhibitor GSK2636771: Application to a pharmacokinetic study in rat plasma.


Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China; Tian Jin JF-Pharmaland Technology Development Co., Ltd, Tianjin, 300457, China. Electronic address: [Email]


A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with one-step protein precipitation extraction method was developed and validated for determination of GSK2636771, a phosphoinositide 3 kinase (PI3K) inhibitor in rat plasma. After protein precipitation with acetonitrile, the chromatographic separation was carried out on a CORTECS UPLC C18 column, with acetonitrile and 0.1 % formic acid in water as mobile phase at a flow rate of 0.30 mL·min-1. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source, with target quantitative ion pairs of m/z 434.2→416.2 for GSK2636771, and 411.2→367.2 for BKM120 (internal standard). The calibration curve was linear over the range of 2.0-8000 ng·mL-1, and the LLOQ was evaluated to be 2.0 ng·mL-1. The accuracy (relative error, RE %) ranged from -3.4 % to 4.7 %, and the intra- and inter-day precision were within 15 %, and with the mean extraction recovery 82.1-89.3 %. The validated method described a quantification method of GSK2636771 in detail for the first time and applied to a pharmacokinetic study after oral administration of GSK2636771 at low, medium and high doses in rats. The mean plasma concentration versus time profiles of GSK2636771 showed a dose-dependent relationship at different doses.


GSK2636771,LC–MS/MS,Pharmacokinetics,Phosphoinositide 3 kinase,

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