Bioanalysis of tolvaptan,a novel AVP‐V2 receptor antagonist in human plasma by a novel LC‐ESI‐MS/MS method: a pharmacokinetic application in healthy South Indian male subjects |
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| Authors: | Venkata Ramu Derangula Nageswara Rao Pilli Babu Rao Bhukya Chalapathi Rao Pulipati Vinayender Adireddy Venkateswarlu Ponneri |
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| Affiliation: | 1. Research Studies, Rayalaseema University, Kurnool, India;2. Wellquest Clinical Research Laboratories, Hyderabad, India;3. University College of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Hyderabad, India;4. Sree College of pharmacy, Khmmam, India;5. Analytical and Environmental Chemistry Division, Department of Chemistry, Sri Venkateswara University, Tirupati, India |
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| Abstract: | A simple, rapid and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS) assay method is proposed for the determination of tolvaptan in human plasma samples using tolvaptan d7 as internal standard (IS). Analyte and the IS were extracted from 100 μL of human plasma via simple liquid–liquid extraction. The chromatographic separation was achieved on a C18 column using a mixture of methanol and 0.1% formic acid buffer (80:20, v/v) as the mobile phase at a flow rate of 1.0 mL/min. The calibration curve obtained was linear (r2 ≥ 0.99) over the concentration range of 0.05–501 ng/mL. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The intra‐day and inter‐day precision (coefficient of variation) and accuracy results in three validation batches across five concentration levels were well within the acceptance limits. A run time of 2.0 min for each sample made it possible to analyze more samples in a short time, thus increasing the productivity. The proposed method was successfully applied to a pharmacokinetic study of 15 mg and 60 mg tolvaptan tablet formulation in healthy South Indian male subjects under fasting condition. Copyright © 2013 John Wiley & Sons, Ltd. |
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| Keywords: | tolvaptan human plasma liquid– liquid extraction LC‐ESI‐MS/MS pharmacokinetics |
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