Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 913, Issue -, Pages 84-89Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2012.11.027
Keywords
Tolvaptan; LC-MS/MS; Human plasma; Pharmacokinetics
Funding
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2012ZX09303014-001]
- Program for Science and Technology Research of Hunan Province [2012WK3044]
- Key Subject Foundation of the Third Xiangya Hospital of Central South University
Ask authors/readers for more resources
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 0.457-1000 ng/mL, with a lower limit of quantification of 0.457 ng/mL. The intra- and inter-day precisions at three concentration levels (0.914, 111 and 800 ng/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. (c) 2012 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available