title: 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.
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 (r(2) ≥ 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.
authors: Research Studies, Rayalaseema University, Kurnool, 518 002, India; Wellquest Clinical Research Laboratories, Ramanthapur, Hyderabad, 500 013, India.
authors: Venkata Ramu
authors: VR
authors: Derangula
authors: Nageswara Rao
authors: NR
authors: Pilli
authors: Babu Rao
authors: BR
authors: Bhukya
authors: Chalapathi Rao
authors: CR
authors: Pulipati
authors: Vinayender
authors: V
authors: Adireddy
authors: Venkateswarlu
authors: V
authors: Ponneri
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D059625:Liquid-Liquid Extraction; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000077602:Tolvaptan; D055815:Young Adult
chemical_list: D001552:Benzazepines; D000077602:Tolvaptan
keywords: LC-ESI-MS/MS; human plasma; liquid-liquid extraction; pharmacokinetics; tolvaptan