Cyanide trapping of iminium ion reactive intermediates followed by detection and structure identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Chemical Research in Toxicology
Dayana ArgotiEric Yang

Abstract

Secondary and tertiary alicyclic amines are widely found in pharmaceuticals and environmental compounds. The formation of iminium ions as reactive intermediates in the metabolic activation of alicyclic amines has previously been investigated in radiometric assays where radiolabeled cyanide is typically employed. In this paper, we report a relatively high throughput LC-MS/MS method for the detection of the nonradiolabeled cyanide adduct formed in rat or human liver microsomal incubations via constant neutral loss scan followed by structural characterization using product ion scan on a triple quadrupole mass spectrometer. A total of 14 alicyclic amine compounds were investigated with the cyanide trapping LC-MS/MS screen and also with the glutathione (GSH) trapping screen, a well-established and commonly employed technique for reactive metabolite screening. Our results are found to be in general agreement with the previous metabolism reports for these compounds, demonstrating the effectiveness, speed, and simplicity of the cyanide trapping LC-MS/MS method to study the iminium ion intermediates from alicyclic amines and its complementarities to GSH trapping method for reactive metabolite screenings.

References

May 1, 1971·Southern Medical Journal·F J Kane, L P Moore
Nov 1, 1994·Journal of Pharmaceutical and Biomedical Analysis·L W WhitehouseJ Zamecnik
Jul 1, 1994·European Journal of Drug Metabolism and Pharmacokinetics·J W Gorrod, G Aislaitner
Nov 4, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Amit S KalgutkarCornelis E C A Hop

❮ Previous
Next ❯

Citations

Jun 23, 2007·Analytical and Bioanalytical Chemistry·Roland F Staack, Gérard Hopfgartner
Oct 19, 2006·Pharmaceutical Research·Yuan ChenWilliam L Fitch
Apr 8, 2011·Chemical Research in Toxicology·Feng LiXiaochao Ma
Dec 24, 2010·Drug Metabolism and Pharmacokinetics·Toshihiko Ikeda
Apr 24, 2013·Archives of Toxicology·Alison V M RodriguesIan D Wilson
Feb 25, 2009·Expert Opinion on Drug Metabolism & Toxicology·Bo Wen, William L Fitch
Feb 3, 2007·Expert Opinion on Drug Metabolism & Toxicology·Robert J RileyRichard Weaver
May 26, 2015·Expert Opinion on Drug Metabolism & Toxicology·Mark P Grillo
Sep 24, 2011·Drug Metabolism Reviews·Louis LeungR Scott Obach
Apr 4, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Toshihiko Ikeda
Jan 7, 2016·Chemical Research in Toxicology·Richard A ThompsonDominic P Williams
Jan 18, 2011·Chemico-biological Interactions·W Griffith Humphreys
Nov 16, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jaana E LaineRisto O Juvonen
Dec 23, 2015·Journal of Applied Toxicology : JAT·M José Gómez-LechónM Teresa Donato
Dec 9, 2008·Drug Discovery Today·Ari TolonenOlavi Pelkonen
Oct 24, 2012·Medicinal Research Reviews·Andrew V StachulskiMartin S Lennard
Apr 20, 2011·Rapid Communications in Mass Spectrometry : RCM·Timo Rousu, Ari Tolonen
Nov 11, 2008·International Journal of Pharmaceutics·Misao NishimuraYoshinori Itoh
May 1, 2009·Bioanalysis·Olavi PelkonenHannu Raunio
Sep 10, 2016·ACS Central Science·Tyler B HughesS Joshua Swamidass
Jun 12, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Haruka NishimutaMasashi Yabuki
Sep 29, 2011·Rapid Communications in Mass Spectrometry : RCM·Joanna E Barbara, Jose M Castro-Perez
Sep 13, 2006·Journal of Mass Spectrometry : JMS·Shuguang Ma, Raju Subramanian
Jul 1, 2008·Expert Review of Clinical Pharmacology·Amit S KalgutkarJonathan Bauman
Jan 10, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jim ZhengJeffrey A Silverman
Sep 2, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Toru UsuiSetsuko Komuro
Mar 12, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jonathan N BaumanAmit S Kalgutkar
Jul 17, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Joanna E BarbaraAndrew Parkinson
Feb 23, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Minli ZhangKarthick Vishwanathan
Apr 24, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Amit S KalgutkarHeather Eng

❮ 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.