A sensitive LC assay for the simultaneous determination of centbutindole and its metabolite in rat serum using fluorescence detection

Centbutindole (+/-) 2-gamma-[(p-fluorobenzoyl)propyl]-1, 2, 3, 4, 6, 7, 12, 12a-octahydro-pyrazino (2', 1': 6, 1) pyrido [3, 4-b] indole (I), is a new neuroleptic agent developed by Central Drug Research Institute, India. In the present study, a high performance liquid chromatography (HPLC) assay me thod for the simultaneous assay for I and its metabolite (II) in rat serum was developed and validated. The present method requires only 1 ml of serum with detection levels similar to that reported earlier using 4 ml serum. T his assay has been found to be more suited for pre-clinical as well as phas e IV studies. Linearity was observed between 1.25 and 40 ng/ml for I and 0. 625 and 20 ng/ml for II in rat serum. Recoveries were consistent for both t he analytes over the concentration ranges studied. Variation in intra-and i nter-batch accuracy and precision were within acceptable limits of +/-20% a t lowest limit of quantitation, whereas at higher concentrations it was +/- 15%. The assay method was employed for the study of the pharmacokinetics a nd metabolism of I in rats. The parent compound and its metabolites were qu antitated in serum and could be monitored up to 24 h post dose. (C) 2002 El sevier Science B.V. All rights reserved.