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]carba mate, is a new antifilarial compound being developed by the World Health Organization. In the present study, a HPLC method for the simultaneous estimation of UMF-078 and its metabolites (flubendazole, decarbamoylated flubendazole, UMF060 and decarbamoylated UMF-060) in plasma was developed, validated and applied to pharmacokinetic studies. Linearity was observed between 20 and 1000 ng/ml for decarbamoylated UMF-060 and between 10 and 500 ng/ml for other analytes. Recoveries were consistent over the concentration ranges studied for all the analytes. Variations in intra- and inter-batch accuracy and precision were within acceptable limits of +/-20% at the lowest limit of quantitation, whereas at higher concentrations it was +/-15%. The analytes 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 plasma extracts at -30 degrees C. The assay method was employed to study the pharmacokinetics of hydrochloride salt of UMF-078 in rats. The parent compound and its metabolites viz: decarbamoylated UMF-060, UMF-060 and flubendazole were quantitated in serum and the compounds could be monitored up to 168 h post-dose.
Issar
M
M
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, India.
Nagaraja
N V
NV
Lal
J
J
Paliwal
J K
JK
Gupta
R C
RC
D000818:Animals; D000969:Antinematodal Agents / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000969:Antinematodal Agents; C089375:UMF 078; D008463:Mebendazole