Determination of antifilarial compound UMF-078 and its metabolites in plasma by high-performance liquid chromatography

UMF-078, methyl (+/-)-[5-(alpha-amino-4-fluorobenzyl)benzimidazol-2-yl]carb amate, is a new antifilarial compound being developed by the World Health O rganization. In the present study, a HPLC method for the simultaneous estim ation of UMF-078 and its metabolites (flubendazole, decarbamoylated flubend azole, UMF060 and decarbamoylated UMF-060) in plasma was developed, validat ed and applied to pharmacokinetic studies. Linearity was observed between 2 0 and 1000 ng/ml for decarbamoylated UMF-060 and between 10 and 500 ng/ml f or other analytes. Recoveries were consistent over the concentration ranges studied for all the analytes. Variations in intra- and inter-batch accurac y and precision were within acceptable Limits of +/-20% at the lowest limit of quantitation, whereas at higher concentrations it was +/-15%. The analy tes showed stability up to two freeze-thaw cycles in plasma. No degradation was observed for any of the analytes even after 72 h of storing the dry pl asma extracts at -30 degrees C. The assay method was employed to study the pharmacokinetics of hydrochloride salt of UMF-078 in rats. The parent compo und and its metabolites viz: decarbamoylated UMF-060, UMF-060 and flubendaz ole were quantitated in serum and the compounds could be monitored up to 16 8 h post-dose. (C) 1999 Elsevier Science B.V. All rights reserved.