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Pharmacokinetic studies of a novel tubulin inhibitor SK1326 in rat plasma by UPLC–MS/MS
Author(s) -
Ji Young Seok,
Kim Tae Kon
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4749
Subject(s) - chemistry , chromatography , pharmacokinetics , formic acid , selected reaction monitoring , electrospray ionization , high performance liquid chromatography , electrospray , tandem mass spectrometry , mass spectrometry , acetonitrile , pharmacology , medicine
A sensitive method for quantitation of SK1326 in rat plasma has been established using ultra‐performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI/MS/MS). SK1326 and the internal standard (tramadol) in plasma sample were extracted using acetonitrile. A centrifuged upper layer was then evaporated and reconstituted with a mobile phase of 0.5% formic acid–acetonitrile (35:65, v/v). The reconstituted samples were injected into a C 18 reversed‐phase column. Using MS/MS in the multiple reaction monitoring mode, SK1326 and tramadol were detected without severe interference from the rat plasma matrix. SK1326 produced a protonated precursor ion ([M + H] + ) at m / z 432.3 and a corresponding product ion at m / z 114.4. The internal standard produced a protonated precursor ion ([M + H] + ) at m / z 264.4 and a corresponding product ion at m / z 58.1. Detection of SK1326 in rat plasma by the UPLC–ESI/MS/MS method was accurate and precise with a quantitation limit of 1.0 ng/mL. The validation, reproducibility, stability and recovery of the method were evaluated. The method has been successfully applied to pharmacokinetic studies of SK1326 in rat plasma. The pharmacokinetic parameters of SK1326 were evaluated after intravenous (at a dose of 10 mg/kg) and oral (at a dose of 20 mg/kg) administration of SK1326 in rats. After oral administration (20 mg/kg) of SK1326, the F (fraction absorbed) value was ~77.1%.