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

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• 作者：Qili Zhang ; Danlin Wang ; Meiyan Zhang ; Yunli Zhao ; Zhiguo Yu ; ^{zhiguo-yu@163.com}
• 关键词：2-(2-Hydroxypropanamido) benzoic acid ; Enantiomers ; Prodrugs ; UHPLC&ndash ; MS/MS ; Pharmacokinetics ; Liquid&ndash ; liquid extraction
• 刊名：Journal of Chromatography B
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：1041-1042
• 期：Complete
• 页码：175-182
• 全文大小：1328 K
• 卷排序：1041

文摘

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 C18 column (50 mm × 2.1 mm, 1.7 μm; Thermo, USA), which was protected by a high pressure column prefilter (2 μm) at a flow rate of 0.4 ml/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 4.5 min. The lower limit of quantification of (R)-/(S)-HPABA and prodrugs of (R)-/(S)-HPABA in plasma were 0.01 μg/ml and 0.2 μg/ml, respectively. (S)-HPABA showed significantly higher AUC, Cmax and a longer t1/2 than (R)-HPABA, indicating higher bioavailability of the (S)-HPABA. Additionally, inversion between HPABA enantiomers was not observed in rats. (R)-/(S)-HPABA showed higher Cmax and AUC than those of their prodrugs. However, the values of t1/2 of prodrugs were higher than those of (R)-/(S)-HPABA. Furthermore, the higher Vz values of prodrugs might improve the targeting of (R)-/(S)-HPABA in rat tissues.