Simultaneous determination of perhexiline and its monohydroxy metabolites in biological fluids by gas chromatography-electron-capture detection

Journal of Chromatography
R G CooperD Lockhart

Abstract

A rapid and sensitive method for the simultaneous determination of perhexiline and its cis-4-axial and trans-4-equatorial monohydroxy metabolites (M1 and M3, respectively) in human plasma, urine and bile is described. The assay utilises a single diethyl ether extraction, heptafluorobutyric acid anhydride derivatisation and separation and detection by gas chromatography-electron-capture detection. The limits of detection are 0.1 microgram/ml for perhexiline and 0.025 microgram/ml for the M1 and M3 metabolites. This method has been used in a five-day kinetic study of three healthy adult males who ingested a single 300-mg dose of perhexiline maleate. One of these volunteer subjects exhibited elevated plasma perhexiline and markedly reduced plasma and urinary M1 concentrations together with profoundly prolonged plasma and urinary M1 elimination times when compared with the other two subjects. These differences are thought to be of genetic origin. There were also obvious differences in urinary M3 concentrations which were discussed.

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Citations

Jan 1, 1987·European Journal of Clinical Pharmacology·R G CooperA H Price
Apr 29, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·O BeckP Hjemdahl
Sep 5, 2002·British Journal of Clinical Pharmacology·Benedetta C SallustioRaymond G Morris
Nov 6, 1998·British Journal of Clinical Pharmacology·T J Campbell, K M Williams
Apr 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R G CooperA H Price
Feb 14, 2006·European Journal of Cardiovascular Nursing : Journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology·Sally Inglis, Simon Stewart
Jan 22, 2002·Therapeutic Drug Monitoring·R HusseinR L Rasiah

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