High-Performance Liquid Chromatographic Assay of Perhexiline Maleate in Plasma

A sensitive assay is described for the calcium antagonist perhexiline maleate. Alkalinized plasma was extracted with n-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 5ng 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 3-6hr after drug ingestion in four patients and after 12-18hr in the fifth patient. The mean elimination half-life, measured 24hr after drug ingestion, varied with plasma perhexiline concentration. It was 11.2 ± 2.1hr after the 150-mg dose and 19.1 ± 2.8hr after the 300-mg dose. The mean ratio of areas under the concentration-time curve for the 300- versus 150-mg doses was 5.3:1, suggesting that hepatic metabolism of perhexiline may be saturable and that the bioavailability of perhexiline is dose dependent.