Quantification of tolvaptan in rabbit plasma by LC-MS/MS: Application to a pharmacokinetic study

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• 作者：Kumar S. Moola^a ; ^b ; Bala Sekhara Reddy Challa^c ; ^{baluchalla_99@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{reddysampathu@yahoo.co.uk" class="auth_mail" title="E-mail the corresponding author} ; Chandrasekhar Kothapalli Bannoth^b
• 关键词：Tolvaptan ; LC&ndash ; ESI&ndash ; MS/MS ; Rabbit plasma ; Liquid&ndash ; liquid extraction ; Pharmacokinetics
• 刊名：Journal of Pharmaceutical Analysis
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：5
• 期：6
• 页码：371-377
• 全文大小：1164 K

文摘

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 Cb>18b> analytical column (50 mm×2.1 mm, 3.5 µm) 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 0.10–1000.00 ng/mL and successfully applied to a pharmacokinetic study of healthy rabbits.