Abstract
A sensitive, selective and high-throughput liquid chromatography–tandem mass spectrometry (LC–ESI–MS/MS) method was developed and validated for the quantitation of tolvaptan in rabbit plasma. Sample clean-up involved liquid–liquid extraction (LLE) and chromatography was performed on Zorbax SB C18 analytical column (50mm×2.1mm, 3.5µm) using 0.1% formic acid:methanol (20:80, v/v) as the mobile phase. The parent→product ion transitions for the drug (m/z 449.2→252.1) and IS (m/z 456.2→259.2) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) and positive ion mode. The method was validated over the concentration range of 0.10–1000.00ng/mL and successfully applied to a pharmacokinetic study of healthy rabbits.
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