Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Perhexiline and Cis-Hydroxy-Perhexiline Plasma Concentrations

Therapeutic Drug Monitoring
Ian S WestleyBenedetta C Sallustio

Abstract

The polymorphic nature of cytochrome P450 2D6 has made therapeutic drug monitoring of the anti-anginal agent perhexiline a compulsory step in reducing adverse events associated with plasma concentrations above the therapeutic range (0.15-0.60 mg/L). The aim of this study was to develop a high-performance liquid chromatography-mass spectrometry/mass spectrometry method for the determination of plasma perhexiline concentrations and its major metabolite cis-hydroxy-perhexiline to reduce sample extraction procedures and improve sample turnaround times. The method was validated by determining the precision and accuracy of calibrators and quality control material, comparing quality assurance program samples and patient samples measured by a previously reported liquid-liquid extraction fluorescence (FL) detection high-performance liquid chromatography method and performing matrix effects investigations. Replicates of calibrators at concentrations of 3.00 and 0.05 mg/L demonstrated imprecision of <10.8% and inaccuracy of <8.2% for perhexiline and <10.1% and <4.5% for cis-hydroxy-perhexiline, respectively. All samples measured by the 2 methods (n = 102) demonstrated Deming regression of perhexiline = 1.20 FL + 0.00 (Sy.x = 0.08, 1/slope...Continue Reading

References

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Sep 5, 2002·British Journal of Clinical Pharmacology·Benedetta C SallustioRaymond G Morris
Apr 29, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·O BeckP Hjemdahl
Jan 26, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Benjamin J DaviesBenedetta C Sallustio
Jul 14, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Benjamin J DaviesBenedetta C Sallustio
Aug 4, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Mei ZhangEvan J Begg

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