title: 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.
abstract: Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is an investigational new drug having the capacity for treating ailments in 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-C18column (150 × 4.6 mm i.d., 5 µm) and online identification of the metabolites by Q-TOF-MS equipped with electrospray ionizer. A total of 16 metabolites from IDHP, including 4 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. This article is protected by copyright. All rights reserved.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Lingjian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Jia
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Shixiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Chaoni
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng