High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry.

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Abstract Text:

Bo Wen,Li Ma,Sidney D Nelson,Mingshe Zhu,

A highly sensitive and efficient method has been developed for detection and characterization of glutathione (gamma-glutamyl-cysteinylglycine, GSH)-trapped reactive metabolites using a negative precursor ion (PI) as the survey scan to trigger the acquisition of positive enhanced product ion (EPI) spectra on a triple quadrupole linear ion trap mass spectrometer. The negative precursor ion scan step was carried out monitoring the anion at m/z 272, corresponding to deprotonated gamma-glutamyl-dehydroalanyl-glycine originating from the glutathionyl moiety. Because of the uniqueness and abundance of the anion at m/z 272, this single survey scan exhibited broad utility in the detection of unknown GSH conjugates. Further structural characterization was achieved by analyzing positive MS2 spectra that featured rich fragments without mass cutoff and were acquired in the same liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. The effectiveness and reliability of this approach was evaluated using a number of model compounds in human liver microsomal incubations, including acetaminophen, clozapine, diclofenac, imipramine, meclofenamic acid, and ticlopidine. As a result, the PI-EPI approach revealed the presence of known adducts and, in many instances, identified additional conjugates that had not been reported previously. In comparison to the widely used neutral loss (NL) scanning analysis, this approach provided superior sensitivity and selectivity for different types of GSH conjugates. More importantly, the PI-EPI approach is suitable for high-throughput screening of reactive metabolites in the drug discovery process.

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Publishing Authors By Initials

B Wen,L Ma,SD Nelson,M Zhu,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Analytical chemistry

VOLUME: 80

Page Numbers: 1788-99

Journal Abbreviation: Anal. Chem.

ISSN: 0003-2700

DAY: 6

MONTH: 02

YEAR: 2008

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370536

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry.

AFFILIATION: Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, New Jersey 08543, and Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Anal Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry Related Publications

• Cell signaling by imidazoline-1 receptor candidate, IRAS, and the nischarin homologue.
• Cloning and expression of xeroderma pigmentosum complementation group A cDNA and the identification of its recombinant protein.
• Modification of glycosylation reduces microvilli on rat liver epithelial cells.
• [Aberrant neuronal expression of mitotic protein, tau and Bax in the rat brain after injection of Abeta(25-35) into the amygdala]
• [Application of expressed sequence tag (EST) in parasite genome research]
• [Clinical investigation of the correlation between blood concentration of lactic acid and tissue oxygenation in severely burned patients]
• [Combined detection of K-ras mutation and CA19-9 level in plasma of patients with pancreatic cancer]
• [Comparison of endoscopic irsection and vaporization for superficial bladder cancer]
• [Construction of the prokaryotic expression vector of MTB lhp gene and its expression]
• [Diagnosis and treatment of adrenal medullary hyperplasia (with report of 8 cases)]
• [Effects of Nomega-nitro-L-arginine on photoreceptor apoptosis in inherited retinal degeneration of RCS rats]
• [Effects of lamivudine on cirrhotic patients following chronic hepatitis B]
• [Effects of terrestrial input on the harmful algal bloom area--with aluminum as an example]
• [Experimental study on human reaction of determination and performance in virtual environment]
• [Expression of core-binding factor a1 by human skin fibroblasts induced in vitro]
• [Expression of some active peptides and extracellular matrix in the in vitro cultured tissue engineering skin]
• [Investigation of resection and reconstruction procedure of high-sacra tumors]
• [Mechanism of arsenic trioxide-induced apoptosis in hepatic blastoma cells HepG2]
• [Microzooplankton herbivory during red tide-frequent-occurrence period in spring in the East China Sea]
• [Regulative effects and significance of substance P on the expression of basic fibroblast growth factor of granulation tissue fibroblasts in vitro]
• [Role of NADH-cytochrome b(5) reductase in biosynthesis of thyroid hydrogen peroxide]
• [Study of specific targeting cytotoxicity mediated by anti-CD(3)/anti-CD(20) Diabody]
• [Study on gene mutation in 11 Chinese families with Hailey-Hailey disease]
• [Study on making pneumoconiosis model and method of lung lavage in rabbit]
• [Study on the mutation of human telomeric repeat binding factor 1 gene in malignant hematopoietic cell lines]
• [Successful management of sudden respiratory and heart arrest resulting from severe closed thoracoabdominal trauma: report of one case]
• [The expression and mechanism study of BMP in pleomorphic adenoma]
• [The mutation of anti-CD3 antibody (HIT3a) gene and its expression]
• [The prevention of primary liver cancer by selenium in high risk populations]
• kappa-Opioid receptor stimulation contributes to aortic artery dilation through activation of K(ATP) channel in the rats.