Screening and characterization of reactive metabolites using glutathione ethyl ester in combination with Q-trap mass spectrometry

Journal of Mass Spectrometry : JMS
Bo Wen, William L Fitch

Abstract

The present study describes a new analytical approach for the detection and characterization of chemically reactive metabolites using glutathione ethyl ester (GSH-EE) as the trapping agent in combination with hybrid triple quadrupole linear ion trap mass spectrometry. Polarity switching was applied between a negative precursor ion (PI) survey scan and the positive enhanced product ion (EPI) scan. The negative PI scan step was carried out monitoring the anion at m/z 300, corresponding to deprotonated gamma-glutamyl-dehydroalanyl-glycine ethyl ester originating from the GSH-EE moiety. Samples resulting from incubations in the presence of GSH-EE were cleaned and concentrated by solid-phase extraction, followed by the PI-EPI analysis. Unambiguous identification of GSH-EE-trapped reactive metabolites was greatly facilitated by the unique survey scan of the anion at m/z 300, which achieved less background interference, in particular, from endogenous glutathione adducts present in human liver microsomes. Further structural characterization was achieved by analyzing positive MS(2) spectra that featured rich fragments without mass cutoff and were acquired in the same liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Th...Continue Reading

References

Feb 1, 1992·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·L P DelbressineG L Wagenaars
Sep 1, 1989·Biochemical Pharmacology·C LambertN R Kitteringham
Jun 26, 1982·British Medical Journal·C E Page
Jul 17, 1982·British Medical Journal
Feb 1, 1995·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H JewellB K Park
Jun 1, 1993·Biological Mass Spectrometry·T A Baillie, M R Davis
Jan 5, 2002·Advances in Experimental Medicine and Biology·S D Nelson
Jan 5, 2002·Advances in Experimental Medicine and Biology·W G ChenH G Fouda
Apr 19, 2005·Chemical Research in Toxicology·Christine M DieckhausThomas A Baillie
May 17, 2005·Chemical Research in Toxicology·Jinping GanW Griffith Humphreys
Sep 13, 2006·Journal of Mass Spectrometry : JMS·Shuguang Ma, Raju Subramanian
Dec 16, 2006·Current Drug Metabolism·Ian A Blair

❮ Previous
Next ❯

Citations

Apr 8, 2011·Chemical Research in Toxicology·Feng LiXiaochao Ma
Mar 14, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xiaohai LiTomas Vojkovsky
Apr 12, 2014·PLoS Pathogens·Hendrik Jan ThibautJohan Neyts
Feb 3, 2015·Drug Metabolism Reviews·Bo Wen, Mingshe Zhu
Nov 16, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jaana E LaineRisto O Juvonen
Aug 12, 2009·Journal of Mass Spectrometry : JMS·Ivica Kopriva, Ivanka Jerić
Oct 24, 2012·Medicinal Research Reviews·Andrew V StachulskiMartin S Lennard
Oct 16, 2015·Journal of Medicinal Chemistry·Francisco Lopez-TapiaAndré Alker
Aug 12, 2015·Journal of Pharmaceutical and Biomedical Analysis·Toni LassilaAri Tolonen
Jul 3, 2015·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yu SunShaojiang Song
Nov 29, 2015·Human & Experimental Toxicology·A TailorB K Park
Jul 26, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Liang LiDafang Zhong
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matteo MoriArianna Gelain
Jan 27, 2021·Chemical Research in Toxicology·Tyler B HughesS Joshua Swamidass
Sep 4, 2020·Journal of Chemical Information and Modeling·Tyler B HughesS Joshua Swamidass

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.