Naftopidil (NAF) is used as a racemate to treat benign prostatic hyperplasia (BPH) and to prevent prostate cancer. However, racemic NAF has low bioavailability; therefore, it is commonly administered at higher clinical dosages compared to other therapeutic BPH drugs. Differences in interactions between individual enantiomers and biological macromolecules may result in variations in pharmacokinetics and dispositions. This study aimed to investigate the pharmacokinetics, bioavailability and tissue distributions of NAF enantiomers in rats after intragastric administration of the individual enantiomers. A rapid and sensitive liquid chromatography coupled with triple-quadrupole mass spectrometric method (RRLC-MS/MS) was developed and validated for determination of NAF enantiomers in rat plasma, tissues, urine and feces. After intragastric administration, S(-)-NAF in plasma [maximum concentration (C-max) = 186.4 ng/mL, area under the curve from 0 h to 24 h (AUC(0-24) h) 1 = 877.9 ng h/mL] was significantly higher than that of R(+)- NAF (C-max = 133.2 ng/mL, AHC(0-24) h = 602.1 ng h/mL). Moreover, S(-)-NAF bioavailability was twice that of R(+)-NAF.R(+)-NAF distributions in the prostate, liver, and kidney were significantly higher than S(-)-NAF distributions (R/S ratios of 3.16, 1.33, and 2.90, respectively). These data reveal the stereoselective pharmacokinetic profiles of the two enantiomers in rats. (C) 2015 Elsevier B.V. All rights reserved.