We investigated the pharmacokinetic profile of (R)- and (S)-zaltoprofen (ZPF) in rats using rapid and selective liquid chromatography with solid-phase extraction (SPE). The ZPF enantiomers were extracted from a small volume of plasma (0.2 mL) by means of SPE using cartridges and were analyzed on a Chiralcel OJ-H (4.6 mm × 150 mm, 5 μm) column with ultraviolet detection at 244 nm. The lower limit of quantification of the ZPF enantiomers in plasma was 0.1μg/mL. The validated method was successfully applied to chiral pharmacokinetic studies of oral administration of racemic ZPF to rats. (S)-ZPF showed significantly higher AUC, T(max), and C(max) and a longer half-life than (R)-ZPF, indicating higher bioavailability of the (S)-isomer. A total of 8 samples (about 12% of the total number of samples) were selected for incurred sample reanalysis (ISR). The % difference between the re-assay concentrations and the original concentrations were all less than 15% of their mean values and met the acceptance criteria for ISR.
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