title: The determination of 2-(2-hydroxypropanamido) benzoic acid enantiomers and their corresponding prodrugs in rat plasma by UHPLC-MS/MS and application to comparative pharmacokinetic study after a single oral dose.
abstract: A simple and sensitive UHPLC-MS/MS method was developed and validated to determine the pharmacokinetic profile of 2-(2-hydroxypropanamido) benzoic acid (HPABA) enantiomers and their prodrugs in rat plasma. Separation was performed on a Thermo Syncronis C18column (50mm×2.1mm, 1.7μm; Thermo, USA), which was protected by a high pressure column prefilter (2μm) at a flow rate of 0.4ml/min. Liquid-liquid extraction with ethyl acetate was used to process plasma samples. The separation of two enantiomers, prodrugs of (R)-/(S)-HPABA and internal standard was obtained within a cycle time of 4.5min. The lower limit of quantification of (R)-/(S)-HPABA and prodrugs of (R)-/(S)-HPABA in plasma were 0.01μg/ml and 0.2μg/ml, respectively. (S)-HPABA showed significantly higher AUC, Cmaxand a longer t1/2than (R)-HPABA, indicating higher bioavailability of the (S)-HPABA. Additionally, inversion between HPABA enantiomers was not observed in rats. (R)-/(S)-HPABA showed higher Cmaxand AUC than those of their prodrugs. However, the values of t1/2of prodrugs were higher than those of (R)-/(S)-HPABA. Furthermore, the higher Vzvalues of prodrugs might improve the targeting of (R)-/(S)-HPABA in rat tissues.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
authors.forename: Qili
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
authors.forename: Danlin
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang, 110016, China. Electronic address: zhiguo-yu@163.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C000594866:2-(2-hydroxypropanamido)benzoic acid; D001565:Benzoates
keywords: 2-(2-Hydroxypropanamido) benzoic acid; Enantiomers; Liquid–liquid extraction; Pharmacokinetics; Prodrugs; UHPLC–MS/MS