High-performance liquid chromatographic assay of perhexiline maleate in plasma.

Abstract

A sensitive assay is described for the calcium antagonist perhexiline maleate. Alkalinized plasma was extracted with nb-hexane, the organic phase was evaporated, and the residue was dansylated prior to analysis by reversed-phase high-performance liquid chromatography using a fluorescence detector. Perhexiline was resolved from its mono- and dihydroxylated metabolites, and the limit of sensitivity was 5 ng of perhexiline/ml. This limit represents approximately 100 times the sensitivity of the previously described GLC assay. Single-dose pharmacokinetic studies were performed with 150- and 300-mg oral doses of perhexiline maleate in five patients with severe angina pectoris and impaired left ventricular function. Peak plasma perhexiline levels occurred 3-6 hr after drug ingestion in four patients and after 12-18 hr in the fifth patient. The mean elimination half-life, measured 24 hr after drug ingestion, varied with plasma perhexiline concentration. It was 11.2 +/- 2.1 hr after the 150-mg dose and 19.1 +/- 2.8 hr after the 300-mg dose. The mean ratio of areas under the concentration-time curve for the 300-versus 150-mg doses ws 5.3:1, suggesting that hepatic metabolism of perhexiline may be saturable and that the bioavailability of perhexiline is dose dependent.

• Authors: J D Horowitz, P M Morris, O H Drummer, A J Goble, W J Louis
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 70 Issue 3 Pg. 320-2 (Mar 1981) ISSN: 0022-3549 [Print] United States
• PMID: 7264901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperidines
• Perhexiline

Topics

• Aged
• Chromatography, High Pressure Liquid
• Dose-Response Relationship, Drug
• Half-Life
• Humans
• Perhexiline (administration & dosage, blood)
• Piperidines (blood)
• Time Factors