Trace-level quantitation of iralukast in human plasma by microbore liquid chromatography/tandem mass spectrometry.

Abstract

Iralukast (CGP 45715A) is a potent peptido-leukotriene antagonist that is active in various in vitro and animal models for the treatment of asthma. An analytical challenge was to develop a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method with a lower limit of quantitation (LLOQ) of 10 pg/mL for the analysis of iralukast when administered at low doses during clinical trials. Several issues had to be addressed in order to devise a LC/MS/MS assay for the above compound. First, iralukast appeared to be light sensitive and unstable at room temperature under acidic conditions. Second, a LLOQ of 10 pg/mL was needed to support several clinical trials. Third, positive electrospray ionization of iralukast did not yield the necessary sensitivity required for studies in humans. Consequently, LC/MS/MS conditions were optimized for the negative ion mode of detection. Fourth, sample preparation steps proved to be critical to reduce the possibility of microbore HPLC column (50 mm x 1.0 mm i.d.) obstruction, chromatographic deterioration, and matrix-mediated electrospray ion suppression. While our validated method addressed the above challenges, its major drawback was limited sample throughput capability. Nonetheless, plasma concentration-time profiles for patients with moderate asthma after oral administration of 200, 500, 1000, and 5000 microgram/kg/day of iralukast were successfully obtained.

• Authors: T K Majumdar, R Bakhtiar, D Melamed, F L Tse
• Journal: Rapid communications in mass spectrometry : RCM (Rapid Commun Mass Spectrom) Vol. 14 Issue 6 Pg. 476-81 ( 2000) ISSN: 0951-4198 [Print] England
• PMID: 10717659 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright 2000 John Wiley & Sons, Ltd.

Chemical References

• Anti-Asthmatic Agents
• Benzopyrans
• Indicators and Reagents
• Leukotriene Antagonists
• Solutions
• iralukast

Topics

• Anti-Asthmatic Agents (blood, pharmacokinetics)
• Benzopyrans (blood, pharmacokinetics)
• Calibration
• Chromatography, Liquid
• Freezing
• Humans
• Indicators and Reagents
• Leukotriene Antagonists (blood, pharmacokinetics)
• Mass Spectrometry
• Quality Control
• Reference Standards
• Solutions