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-C column (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.

Metabolite identification of tanshinol borneol ester in rats by high‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight mass spectrometry

“…Hence, M7a and M7b were speculated to be the glucuronidation products of DSS. Moreover, the specific MS/MS information on M7 was in accordance with an earlier study (Yang et al, ). Based on the statement above, M7a and M7b were putatively assigned as 3‐(3‐hydroxyphenyl‐4‐ O‐ glucuronyl)‐2‐hydroxypropanoic acid and 3‐(3‐ O‐ glucuronyl‐4‐hydroxyphenyl)‐2‐hydroxypropanoic acid (Figure S3).…”

“…In addition, the product ion at m / z 211.0603 was consistent with the quasi‐molecular ion of O‐ methylated DSS, according to a previous report (Wang et al, ). The ion at m / z 165.0578 was generated via the loss of HCOOH from the ion at m / z 211.0603 (Yang et al, ), while the fragment ion at m / z 153.1277 was tentatively supposed to be 1 mole of borneol. The information on these ions indicated that the appearance of O‐ methylated DSS was due to the breaking of the ester bond in DBZ to form borneol and DSS, and then O‐ methylation conjugation occurred on one of the hydroxyl groups on the phenyl ring of DSS (Supporting Information, Figure S1).…”

“…This subtracted 16 Da from DSS, and yielded product ions such as m / z 163.0395 [M − H − H 2 O] − , m / z 135.0511 [M − H − HCOOH] − and m / z 119.0493 [M − H − H 2 O ‐CO 2 ] − . From the reported literature (Jarrell et al, ; Yang et al, ), M10 was a dehydroxylation metabolite of DSS and was preliminarily identified as 2‐hydroxy‐3‐(4‐hydroxyphenyl) propanoic acid (Figure S4).…”

Metabolite Profiling of Microwave-Assisted Sargassum fusiforme Extracts with Improved Antioxidant Activity Using Hybrid Response Surface Methodology and Artificial Neural Networking-Genetic Algorithm

“…Based on the fragmentation pattern, compounds 1 – 2 were previously identified as gallic acid and vanillic acid, respectively [ 21 ]. Compound 3 , reported in Dasya sp., yielded two daughter ions at m/z 179.03 (isopropanol group) and m/z 123.04 by cleaving the α, β carbon–carbon bond, and was identified as isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate [ 37 ]. Compound 4 (3,4-dihydroxyphenylglycol) yielded a precursor ion at m/z 169.0506, which was further fragmented into two major daughter ions at m/z 151.03 (losing H 2 O) and 123.00 (losing CO).…”

A target‐group‐change couple with mass defect filtering strategy to identify the metabolites of “Dogel ebs” in rats plasma, urine and bile

“…Although there are many studies on the chemical constituents of “Dogel ebs” , at present, it is essential to obtain its pharmacokinetic parameters and metabolism information to fully understand the pharmacological effects and mechanism of “Dogel ebs.” Unfortunately, the identification of metabolites and illustration of its metabolic patterns have not yet been studied, except the pharmacokinetics investigations on matrine , which restricted the therapeutic applications and development of “Dogel ebs.” In order to clarify the metabolic mechanism of “Dogel ebs,” a target‐group‐change couple with mass defect filtering strategy was proposed based on high performance liquid chromatography–quadrupole exactive Orbitrap mass spectrometry (HPLC‐Q‐Exactive/MS) and Compound Discoverer software. As previously reported , Compound Discoverer software could provide elemental composition assignment, exact mass measurement, and fragmentation information in Traditional Chinese medicines and their metabolites in biological matrices .…”