Metabolism studies on prim‐O‐glucosylcimifugin and cimifugin in human liver microsomes by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry

Abstract

Prim-O-glucosylcimifugin (PGCN) and cimifugin (CN) are major constituents of Radix Saposhnikoviae that have antipyretic, analgesic and anti-inflammatory pharmacological activities. However, there were few reports with respect to the metabolism of PGCN and CN in vitro. In this paper, we describe a strategy using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for fast analysis of the metabolic profile of PGCN and CN in human liver microsomes. In total, five phase I metabolites of PGCN, seven phase I metabolites and two phase II metabolites of CN were identified in the incubation of human liver microsomes. The results revealed that the main phase I metabolic pathways of PGCN were hydroxylation and hydrolysis reactions. The phase I metabolic pathways of CN were found to be hydroxylation, demethylation and dehydrogenation. Meanwhile, the results indicated that O-glucuronidation was the major metabolic pathway of CN in phase II metabolism. The specific UDP-glucuronosyltransferase (UGT) enzymes responsible for CN glucuronidation metabolites were identified using recombinant UGT enzymes. The results indicated that UGT1A1, UGT1A9, UGT2B4 and UGT2B7 might play major roles in the glucuronidation of CN. Overall, this study may be useful for the investigation of metabolic mechanism of PGCN and CN, and it can provide reference and evidence for further pharmacodynamic experiments. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid analysis of Saposhnikovia divaricate decoction metabolism in rats by UHPLC–Q‐TOFMS and multivariate statistical analysis

“…Multivariate statistical analysis allowed metabolites of SDD to be identified faster and allowed us to visually recognize key metabolites, even those with lower concentrations. Using this method, more metabolites were identified compared with previous studies on metabolism of SDD or monomer compounds in SDD (Li et al, ; Jia et al, ).…”

“…So far, there have been few reports on the metabolism of orally administered Saposhnikovia divaricate decoction (SDD). An existing study on the in vivo metabolism of compounds identified in SDD was restricted to only two main compounds (Jia et al, ). Understanding the absorbed constituents and metabolites of TCMs is crucial for the determination of their pharmacologically active substances.…”

Metabolites study on 5‐O‐methylvisammioside in vivo and in vitro by ultra high performance liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry

“…The third step was to identify the chemical structure of metabolites based on the accurate mass measurement, relevant biotransformation knowledge, and reported fragmentation patterns of parent drug and MS/MS spectrum of metabolites. Finally, metabolites were obtained by comparing the extracted ion chromatograms and base peak chromatograms of the sample group with those of the blank group using Peakview software 2.2 . Furthermore, Clog P that can avoid many isomers usually being identified as a single compound was calculated by the program Chemdraw Ultra 14.0.…”

“…After losing two CH 3 groups, the fragment ion at m / z 273.1104 produced fragment ion at m / z 243.0633. Fragment ion at m / z 273.1103 yielded other fragment ions at m / z 231.0635, 205.0481, 189.0540 through dropping continuously C 3 H 6 , C 2 H 2 , and O . And the fragment ion at m / z 231.0635 get product ion at m / z 217.0422 via losing CH 2 .…”

“…Radix Saposhnikoviae (RS), called “Fang Feng” in Chinese, is the dried roots of Saposhnikovia divaricata (Turcz.) Schischk . It is a kind of important Traditional Chinese Medicine (TCM) with anti‐inflammatory and anti‐spasm activities and is widely used for the treatment of pyrexia, rheumatism, headache, vertigo, generalized aching, and convulsion .…”