Enantioseparation and determination of alminoprofen in rat plasma and its application to a stereoselective pharmacokinetic study.

Abstract An enantioselective study of alminoprofen (AMF) in rat plasma was performed by a rapid, specific and sensitive chiral liquid chromatography–tandem mass spectrometry (LCM S/MS) method. A homemade β-cyclodextrin (β-CD) derivatized based chiral column and a commercial polysaccharide type chiral column were selected and evaluated. The former one per-4-chlorophenylcarbamate-β-CD bonded chiral stationary phase (CSP) which was synthesized in our lab produced the enhanced enantioselective separation. The dextro-ketoprofen (d-KTF) was selected as the internal standard (IS). The approach was linear in the concentration ranges of 1.00–20000.0 ng mL−1 (r2≥0.99) for each enantiomer. The mean recoveries of R‐(−)‐ and S‐(+)‐AMF at three spiked levels of 2.00, 1000.0 and 16000.0 ng mL−1 ranged from 92.0 %–96.1 %, and the intra-day and inter-day relative standard deviations (RSDs) were within 8.9 %. The lower limit of quantification (LLOQ) values of R‐(−)‐ and S‐(+)‐AMF in rat plasma matrices were both 1.00 ng mL−1. The established method was successfully applied to a stereoselective pharmacokinetic study of AMF enantiomers in rat plasma following oral administration. The pharmacokinetic results revealed that S‐(+)‐AMF displayed prominently higher Cmax and AUC values than R‐(−)‐enantiomer.