Determination of a cyclic hexapeptide (L-743 872), a novel pneumocandin antifungal agent in human plasma and urine by high-performance liquid chromatography with fluorescence detection

Abstract

A method based on high-performance liquid chromatography (HPLC) with fluorescence detection for the determination of a novel peptide antifungal agent, L-743 872 (I), in human plasma and urine is presented. Drug and internal standard were extracted from plasma and urine using diol solid-phase extraction columns and selectively eluted using a solution of trifluroacetic acid and ammonium hydroxide in methanol. Chromatography was performed on a wide pore C8 column and detection was by fluorescence. Loss of drug from urine due to adsorption to plastic surfaces was prevented by the addition of bovine serum albumin (0.5% final concentration). The range of the standard line was 10 to 1000 ng/ml for both matrices. The recovery of drug from plasma and urine was 76% and 84%, respectively. The assay was used to measure drug concentrations in human plasma and urine after the administration of intravenous (IV) doses of I.