Quantification of the transporter substrate fexofenadine in cell lysates by liquid chromatography/tandem mass spectrometry.

Colleen A. Flynn, Yazen Alnouti, Gregory A. Reed

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Drug-drug interactions at transporters present a significant and under-investigated clinical problem. Investigations of specific transporter functions and screening for potential drug-drug interactions, both in vitro and especially in vivo, will require validated experimental probes. Fexofenadine, an approved, well-tolerated drug, is a promising probe for studies of membrane transporter function. Although fexofenadine pharmacokinetics are known to be controlled by transporters, the contributions of individual transporters have not been defined. We have developed a rapid, specific, and sensitive analytical method for quantitation of fexofenadine to support this work. This liquid chromatography/tandem mass spectrometry (LC/MS/MS) method quantifies fexofenadine in cell lysates from in vitro studies using cetirizine as the internal standard. Cell lysates were prepared for analysis by acetonitrile precipitation. Analytes were then separated by gradient reversed-phase chromatography and analyzed by tandem mass spectrometry using the m/z 502.17/466.2 transition for fexofenadine and m/z 389.02/201.1 for cetirizine. The method exhibited a linear dynamic range of 1-500 ng/mL for fexofenadine in cell lysates. The lower limit of quantification was 1 ng/mL with a relative standard deviation of less than 5%. Intra- and inter-day precision and accuracy were within the limits presented in the FDA guidelines for bioanalysis. We also will validate this method to support not only the quantification of fexofenadine, but also other probe drugs for drug-drug interaction studies. This method for quantification will facilitate the use of fexofenadine as a probe drug for characterization of transporter activity.

Original languageEnglish (US)
Pages (from-to)2361-2366
Number of pages6
JournalRapid communications in mass spectrometry : RCM
Volume25
Issue number16
StatePublished - Aug 30 2011

Fingerprint

fexofenadine
Liquid chromatography
Tandem Mass Spectrometry
Liquid Chromatography
Mass spectrometry
Drug interactions
Substrates
Drug Interactions
Pharmaceutical Preparations
Cetirizine
Preclinical Drug Evaluations
Pharmacokinetics
Membrane Transport Proteins
Reverse-Phase Chromatography
Chromatography

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Quantification of the transporter substrate fexofenadine in cell lysates by liquid chromatography/tandem mass spectrometry. / Flynn, Colleen A.; Alnouti, Yazen; Reed, Gregory A.

In: Rapid communications in mass spectrometry : RCM, Vol. 25, No. 16, 30.08.2011, p. 2361-2366.

Research output: Contribution to journalArticle

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