Buspirone, fexofenadine, and omeprazole: Quantification of probe drugs and their metabolites in human plasma

Parul Gor, Yazen Alnouti, Gregory A. Reed

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Probe drugs are critical tools for the measurement of drug metabolism and transport activities in human subjects. Often several probe drugs are administered simultaneously in a " cocktail" This cocktail approach requires efficient analytical methods for the simultaneous quantitation of multiple analytes. We have developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three probe drugs and their metabolites in human plasma. The analytes include omeprazole and its metabolites omeprazole sulfone and 5′-hydroxyomeprazole; buspirone and its metabolite 1-[2-pyrimidyl]-piperazine (1PP); and fexofenadine. These analytes and the internal standard lansoprazole were extracted from plasma using protein precipitation with acetonitrile. Gradient reverse-phase chromatography was performed with 7.5. mM ammonium bicarbonate and acetonitrile, and the analytes were quantified in positive ion electrospray mode with multiple reaction monitoring. The method was validated to quantify the concentration ranges of 1.0-1000. ng/ml for omeprazole, omeprazole sulfone, 5′-hydroxyomeprazole, and fexofenadine; 0.1-100. ng/ml for buspirone, and 1.0-100. ng/ml for 1PP. These linear ranges span the plasma concentrations for all of the analytes from probe drug studies. The intra-day precision was between 2.1 and 16.1%, and the accuracy ranged from 86 to 115% for all analytes. Inter-day precision and accuracy ranged from 0.3 to 14% and from 90 to 110%, respectively. The lower limits of quantification were 0.1. ng/ml for buspirone and 1. ng/ml for all other analytes. This method provides a fast, sensitive, and selective analytical tool for quantification of the six analytes in plasma necessary to support the use of this probe drug cocktail in clinical studies.

Original languageEnglish (US)
Pages (from-to)1127-1135
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume55
Issue number5
DOIs
StatePublished - Jul 15 2011

Keywords

  • Buspirone
  • Fexofenadine
  • Human plasma
  • Omeprazole
  • Probe drug cocktail

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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