title: Determination of naftopidil enantiomers in rat plasma using chiral solid phases and pre-column derivatization high-performance liquid chromatography.
abstract: Two bioanalytical HPLC methods (chiral solid phases (CSPs) HPLC and pre-column derivatization HPLC) were developed and validated for the determination of naftopidil enantiomers in rat plasma. Analytes were extracted from biomaterials by liquid-liquid extraction. The pre-column derivatization HPLC method employed (+)-diacetyl-L-tartaric anhydride (DATAN) as the pre-column derivatization reagent, and subsequent separation of diastereomers was conducted on an Agilent Hypersil ODS column with a mixture of methanol-acetonitrile-phosphate buffer (pH 4.1; 20 mM) (40:30:30, v/v/v) flowing at 1 mL/min as the mobile phase. The CSPs HPLC method utilized a Chiralpak IA column with a mobile phase of methanol-acetonitrile-acetate buffer (pH 5.3; 5 mM) (50:25:25, v/v/v) flowing at 0.5 mL/min. In both methods, the analytes were monitored using a fluorescence detector with an excitation wavelength of 290 nm and an emission wavelength of 340 nm. Both methods were consistent (RSD<15% by the derivatization method and<10% by the CSPs method) and linear (r>9950). Compared to the pre-column derivatization method, the CSPs method had lower quantification limits (10.6/9.6 ng/mL of (+)-/(-)-naftopidil by derivatization method and 1.1/1.8 ng/mL of (+)-/(-)-naftopidil by CSPs method), and was simpler to carry out. The validated CSPs method was successfully applied in a pharmacokinetic study of naftopidil enantiomers in rats, which showed that pharmacokinetic parameters of (+)- and (-)-NAF after intravenous administration of (±)-NAF were similar.
authors.affiliation: Drug Research Center of Guangzhou Medical College, Guangzhou, China.
authors.forename: Xiawen
authors.initials: X
authors.lastname: Liu
authors.forename: Yunying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mu
authors.initials: M
authors.lastname: Yuan
authors.forename: Yinxiang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D008297:Male; D009281:Naphthalenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D010879:Piperazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D009281:Naphthalenes; D010879:Piperazines; C064357:naftopidil