Use of cyclic ion mobility spectrometry (cIM)-mass spectrometry to study the intramolecular transacylation of diclofenac acyl glucuronide
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Author(s)
Type
Journal Article
Abstract
1-β-O-Acyl-glucuronides (AGs) are common metabolites of carboxylic acid-containing xenobiotics, including, e.g., many nonsteroidal anti-inflammatory drugs (NSAIDs). They are of concern to regulatory authorities because of the association of these metabolites with the hepatotoxicity that has resulted in drug withdrawal. One factor in assessing the potential risk posed by AGs is the rate of transacylation of the biosynthetic 1-β-O-acyl form to the 2-, 3-, and 4-O-acyl isomers. While transacylation can be measured using 1H NMR spectroscopy or liquid chromatography-mass spectrometry (LC-MS), the process can be time consuming and involve significant method development. The separation of these positional isomers by ion mobility spectrometry (IMS) has the potential to allow their rapid analysis, but conventional instruments lacked the resolving power to do this. Prediction of the collision cross section (CCS) using a machine learning model suggested that greater IMS resolution might be of use in this area. Cyclic IMS was evaluated for separating mixtures of isomeric AGs of diclofenac and was compared with a conventional ultraperformance liquid chromatography (UPLC)-MS method as a means for studying transacylation kinetics. The resolution of isomeric AGs was not seen using a conventional traveling wave IMS device; however, separation was seen after several passes around a cyclic IMS. The cyclic IMS enabled the degradation of the 1-β-O-acyl-isomer to be analyzed much more rapidly than by LC-MS. The ability of cyclic IMS to monitor the rate of AG transacylation at different pH values, without the need for a prior chromatographic separation, should allow high-throughput, real-time, monitoring of these types of reactions.
Date Issued
2021-05-13
Online Publication Date
2022-08-24T13:34:55Z
Date Acceptance
2021-04-12
ISSN
0003-2700
Publisher
American Chemical Society
Start Page
7413
End Page
7421
Journal / Book Title
Analytical Chemistry
Volume
93
Issue
20
Copyright Statement
© 2021 The Authors. Published by American Chemical Society. This work is published under CC BY-NC-ND licence.
Identifier
https://pubs.acs.org/doi/10.1021/acs.analchem.0c04487
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Subjects
Science & Technology
Physical Sciences
Chemistry, Analytical
Chemistry
REACTIVITY
Diclofenac
Glucuronides
Ion Mobility Spectrometry
Mass Spectrometry
Glucuronides
Diclofenac
Mass Spectrometry
Ion Mobility Spectrometry
Science & Technology
Physical Sciences
Chemistry, Analytical
Chemistry
REACTIVITY
Analytical Chemistry
0301 Analytical Chemistry
0399 Other Chemical Sciences
Publication Status
Published
Date Publish Online
2021-05-13