Identification of metabolites of isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate in rats by high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

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• 作者：Lingjian Yang ; Pu Jia ; Qian Li ; Shixiang Wang ; Jing Wang ; Yajun Bai ; Xiaoxiao Wang ; Chaoni Xiao ; Jie Yu ; Peng Zhang and Xiaohui Zheng
• 刊名：Biomedical Chromatography
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：30
• 期：7
• 页码：1042-1051
• 全文大小：445K
• ISSN：1099-0801

文摘

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is an investigational new drug having the capacity for treating ailments in the cardiovascular and cerebrovascular system. In this work, a rapid and sensitive method using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF-MS) was developed to reveal the metabolic profile of IDHP in rats after oral administration. The method involved pretreatment of the samples by formic acid–methanol solution (v/v, 5:95), chromatographic separation by an Agilent Eclipse XDB-C₁₈ column (150 × 4.6 mm i.dx., 5 μm) and online identification of the metabolites by Q-TOF-MS equipped with electrospray ionizer. A total of 16 metabolites from IDHP, including four phase I metabolites and 12 phase II metabolites, were detected and tentatively identified from rat plasma, urine and feces. Among these metabolites, Danshensu (DSS), a hydrolysis product of IDHP, could be further transformed to 11 metabolites. These results indicated that DSS was the main metabolite of IDHP in rats and the major metabolic pathways of IDHP in vivo were hydrolysis, O-methylation, sulfation, glucuronidation and reduction. The results also demonstrated that renal route was the main pathway of IDHP clearance in rat. The present study provided valuable information for better understanding the efficacy and safety of IDHP. Copyright