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Loxoprofen sodium (LOX) is a propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), existing in the form of four stereoisomers. The main metabolites of LOX in vivo were trans - and cis -alcohol, each consisting of four stereoisomers. The objectives of the present study were to examine the selective pharmacokinetic behavior of LOX stereoisomers and stereoselective formation of its alcohol metabolites in rats based on a chiral liquid chromatographytandem mass spectrometry (LC-MS/MS) method by using an FLM Chiral NQ-RH column, which was reported for the first time. The significant difference in pharmacokinetic parameters of four stereoisomers indicated that stereoselective behavior has occurred in rats after oral administration of LOX. (1′ S ,2 S)-LOX showed the highest concentration among the four stereoisomers in both plasma and urine samples. Trans - and cis -alcohol metabolites of LOX were also detected in plasma and urine, and trans -alcohol was found to be primary and the stereoisomeric fractions (SF s) of its four stereoisomers at different times were calculated. Examination of the stereoisomeric composition indicated a stereo preference for (2 S)-configuration with respect to trans -alcohol formation. The overall results of the present study revealed the enantioselective pharmacokinetic properties of LOX stereoisomers in rats, which provided a means to advance understanding of the complex pharmacokinetic of LOX. [ABSTRACT FROM AUTHOR]