title: Enantiospecific determination of naftopidil by RRLC-MS/MS reveals stereoselective pharmacokinetics and tissue distributions in rats.
abstract: 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 24h (AUC(0-24 h)) = 877.9 ng h/mL] was significantly higher than that of R(+)-NAF (C(max) = 133.2 ng/mL, AUC(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.
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Xiawen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Xingfei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Rong
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Cardiovascular Disease, Guangzhou 510260, China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Luo
authors.affiliation: Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510130, China.
authors.forename: Jiewen
authors.initials: J
authors.lastname: Guo
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Huang
authors.affiliation: Guangzhou Medical University, Guangzhou 510182, China. Electronic address: mryuanmu838@sina.com.
authors.forename: Mu
authors.initials: M
authors.lastname: Yuan
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D008297:Male; D009281:Naphthalenes / Q000737:chemistry* / Q000493:pharmacokinetics*; D010879:Piperazines / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution / Q000502:physiology*
chemical_list: D009281:Naphthalenes; D010879:Piperazines; C064357:naftopidil
keywords: Bioavailability; Naftopidil enantiomer; Pharmacokinetics; RRLC-MS/MS; Tissue distribution