title: A rapid and sensitive UHPLC-MS/MS method for quantification of 2-(2-hydroxypropanamido) benzoic acid in rat plasma: application to a pharmacokinetic study.
abstract: A rapid, sensitive and high throughput UHPLC-MS/MS method was established and validated to assay the concentration of 2-(2-hydroxypropanamido) benzoic acid (HPABA), a promising anti-inflammatory drug, in rat plasma. Plasma samples were processed by liquid-liquid extraction with ethyl acetate and separated on a Shim-pack XR-ODS C18 column (75 mm×3.0 mm, 2.2 μm) at an isocratic flow rate of 0.4 mL/min using acetonitrile-0.1% formic acid in water (50:50, v/v) as mobile phase, and total run time was 2 min. MS/MS detection was accomplished in multiple reaction monitoring (MRM) mode with positive electrospray ionization. The calibration curve was linear over the concentration range of 0.01-50 μg/mL with lower limit of quantification of 0.01 μg/mL. The intra- and inter-day precisions were below 8.5% in terms of relative standard deviation (RSD), and the accuracy was within ±4.0% in terms of relative error (RE). Extraction recovery, matrix effect and stability were satisfactory in rat plasma. The developed method was successfully applied to a pharmacokinetic study of HPABA following intragastric administration of 25, 50, 100mg/kg and an intravenous injection at a dose of 12.5 mg/kg to Sprague-Dawley rats. Results indicated that HPABA had linear pharmacokinetic properties within the tested intragastric dosage range and the absolute bioavailability was above 59.1%.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; School of Pharmacy, Jilin Medical College, 5 Jilin Street, Fengman District, Jilin 132013, China.
authors.forename: Heyun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: An
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: zhiguo-yu@163.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000493:pharmacokinetics; D001565:Benzoates / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: C000594866:2-(2-hydroxypropanamido)benzoic acid; D000893:Anti-Inflammatory Agents; D001565:Benzoates
keywords: 2-(2-Hydroxypropanamido) benzoic acid; Liquid–liquid extraction; Pharmacokinetics; Rat; UHPLC–MS/MS