Development of a LC-MS/MS-based method for determining metolazone concentrations in human plasma: Application to a pharmacokinetic study

Yen An Chen, Kuang Yang Hsu

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4 Citations (Scopus)

Abstract

In this study, a method was developed and validated for the quantification of metolazone in human plasma samples. This method involves high-performance liquid chromatography coupled with tandem mass spectrometry and is more sensitive, selective and rapid than currently available methods. Chromatography was performed using a Phenomenex® Luna C18 column (100 mm x 2.0 mm, 5 μm, 100 Å) with an isocratic mobile phase of 0.1% formic acid:acetonitrile (40:60, v/v) and zaleplon as an internal standard. The drug and internal standard were extracted by liquid-liquid extraction and analyzed by mass spectrometry in the multiple reaction monitoring mode by using m/z values of 366.20/259.10 for metolazone and 306.20/235.60 for zaleplon. The calibration curve was linear over metolazone concentrations ranging from 0.02 ng/mL to 15 ng/mL. The lower limit of quantification was 0.02 ng/mL. Intra- and inter-assay precisions were 0.9-4.8% and 4.2-6.3%, respectively. The intra- and inter-assay accuracies in quantifying metolazone were 97.5-102.3% and 99.2-104.0%, respectively. Metolazone and zaleplon were eluted within 3.6 minutes, and the retention time was 1.75 minutes for metolazone and zaleplon. The validated method was successfully applied to a pharmacokinetic study of metolazone in human plasma.

Original languageEnglish
Pages (from-to)154-159
Number of pages6
JournalJournal of Food and Drug Analysis
Volume21
Issue number2
DOIs
Publication statusPublished - Jun 2013

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Keywords

  • Liquid chromatography
  • Mass spectrometry
  • Metolazone
  • Pharmacokinetic study

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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