Application of an Improved HPLC Perhexiline Assay to Human Plasma Specimens

Abstract

Abstract The analysis of perhexiline in plasma offers an important contribution to the management of patients prescribed such therapy for refractory angina pectoris. Perhexiline has properties and complexities of non-linear kinetics and is subject to genetically predetermined metabolic variants in hydroxylation. The present communication describes a refinement of a previous high performance liquid chromatographic fluorescence method and the application of this method in the therapeutic monitoring of 100 patients at steady-state. The method described is sensitive, accurate and precise, with intra-assay CV's of 2. 1%, 1.4% and 3.7% at concentrations of 150, 750 and 1500 μg/L, and between-assav CV's of 5.7%, 4.7% and 5.8% at 50, 1000 and 3000 μg/L, respectively. The review of patient specimens received in our therapeutic drug monitoring laboratory, suggested that approximately 6% appear to belong to the “poor-hydroxvlation” metabolic sub-population, with a further 16% attaining steady-state plasma perhexiline concentrations above the “therapeutic range” of 150 to 600 μg/L following standard dosage schedules of 100 to 200 mg/day.