LC–MS/MS determination of buparlisib,a phosphoinositide 3 kinase inhibitor in rat plasma: Application to a pharmacokinetic study |
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Authors: | Jingyun Wang Meng Ming Lin Yu Guangliang Chen Nan Hao Yuqi Meng Lina Fang |
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Institution: | 1. College of Public Health, Shenyang Medical College, Shenyang, China;2. Office of Academic Affairs, Shenyang Medical College, Shenyang, China;3. College of Basic Medical Science, Shenyang Medical College, Shenyang, China;4. College of Pharmacy, Shenyang Medical College, Shenyang, China |
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Abstract: | Buparlisib is a selective phosphoinositide 3 kinase inhibitor currently evaluated in clinical trials. We developed and validated an LC–MS/MS coupled with a one-step protein precipitation extraction method for the quantitation of buparlisib in rat plasma. After protein precipitation with acetonitrile, the plasma sample was analyzed using a Cortecs UPLC C18 column, with acetonitrile–0.1% formic acid as the mobile phase system. Mass spectrometric detection was conducted in positive ionization mode, with target quantitative ion pair of m/z 411.2 → 367.2 for buparlisib. The calibration curve showed good linearity (1.0–3000 ng/ml), with acceptable accuracy (RE ranging from ?6.2 to 5.9%) and precision (RSD within 8.2%) values at quality control concentrations. Extraction recovery from plasma was 80.9–88.7% and the matrix effect was negligible (92.6–95.2%). The validated method presented a simple quantification method of buparlisib in detail and utilized it for a pharmacokinetic study at three dose concentrations after oral administration in Wistar rats. |
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Keywords: | buparlisib LC–MS/MS pharmacokinetics phosphoinositide 3 kinase |
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