Chromatographic resolution, chiroptical characterization and urinary excretion of the enantiomers of sulindac

The chromatographic resolution of the enantiomers of sulindac has been achi eved using a Chiralpak AD CSP (10 mu m, 250 x 4.6 mm) with a mobile phase o f hexane: ethanol (85:15 v/v) containing trifluoroacetic acid (0.05 % v/v) at a flow rate of 1.0 mL min(-1). Under these conditions the enantiomers el uted with separation and resolution factors of 1.43 and 2.46 respectively. Semipreparative isolation of the enantiomers and their characterization by circular dichroism spectroscopy and NMR, in the presence of a chiral shift reagent, indicated that the elution order was (-)-(S)- before (+)-(R)-sulin dac. The enantiomeric composition of sulindac in urine following administra tion of the racemic drug to man was determined by sequential achiral-chiral chromatography. Achiral analysis was carried out using a Spherisorb S5 ODS 2 stationary phase (5 mu m, 250 x 4.6 mm) and a mobile phase of aqueous ace tic acid (2 % v/v; pH 3.5): acetonitrile: THF (50:48:2 by volume) at a flow rate of 1.0 mt min(-1). The HPLC eluate containing sulindac (retention tim e 4.9 min) was collected and following workup, the enantiomeric composition of the drug was determined using the CSP. Over the 24 h collection period sulindac was excreted predominantly as the R-enantiomer, but the enantiomer ic composition was found to vary markedly with time which is presumably ass ociated with the complex metabolism of the drug.