title: Development and validation of an LC-MS/MS method for the determination of tolvaptan in human plasma and its application to a pharmacokinetic study.
abstract: Tolvaptan is a selective vasopressin V(2)-receptor antagonist mainly used for the treatment of hyponatremia. This study described the development and validation of an LC-MS/MS method for the determination of tolvaptan in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 2-demethyl tolvaptan (internal standard, IS). Chromatographic separation was performed on a Zorbax XDB C(18) column with an isocratic mobile phase consisting of water (containing 0.1% formic acid) and methanol (25:75, v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring (MRM) transitions were performed at m/z 449.2→252.1 for tolvaptan and m/z 435.2→238.1 for IS. The assay was linear over the concentration range of 0.457-1000ng/mL, with a lower limit of quantification of 0.457ng/mL. The intra- and inter-day precisions at three concentration levels (0.914, 111 and 800ng/mL) were less than 15% and their accuracies were within the range of 97.7-107.8%. The mean recovery ranged from 99.2 to 104.6% and the matrix effect from 89.3 to 99.5%. Tolvaptan was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in healthy volunteers after oral administration of single-dose tolvaptan tablets.
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.forename: Bikui
authors.initials: B
authors.lastname: Zhang
authors.forename: Hongyi
authors.initials: H
authors.lastname: Tan
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Peng
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Li
authors.forename: Panhao
authors.initials: P
authors.lastname: Huang
authors.forename: Mi
authors.initials: M
authors.lastname: Luo
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Zuo
authors.forename: Chengxian
authors.initials: C
authors.lastname: Guo
authors.forename: Guoping
authors.initials: G
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D001552:Benzazepines / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards; D000077602:Tolvaptan; D055815:Young Adult
chemical_list: D001552:Benzazepines; D000077602:Tolvaptan