Document Detail


Small molecule quantification by liquid chromatography-mass spectrometry for metabolites of drugs and drug candidates.
MedLine Citation:
PMID:  21937735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Identification and quantification of the metabolites of drugs and drug candidates are routinely performed using liquid chromatography-mass spectrometry (LC-MS). The best practice is to generate a standard curve with the metabolite versus the internal standard. However, to avoid the difficulties in metabolite synthesis, standard curves are sometimes prepared using the substrate, assuming that the signal for substrate and the metabolite will be equivalent. We have tested the errors associated with this assumption using a series of very similar compounds that undergo common metabolic reactions using both conventional flow electrospray ionization LC-MS and low-flow captive spray ionization (CSI) LC-MS. The differences in standard curves for four different types of transformations (O-demethylation, N-demethylation, aromatic hydroxylation, and benzylic hydroxylation) are presented. The results demonstrate that the signals of the substrates compared with those of the metabolites are statistically different in 18 of the 20 substrate-metabolite combinations for both methods. The ratio of the slopes of the standard curves varied up to 4-fold but was slightly less for the CSI method.
Authors:
Upendra P Dahal; Jeffrey P Jones; John A Davis; Dan A Rock
Related Documents :
22581105 - A platform for characterizing therapeutic monoclonal antibody breakdown products by 2d ...
20355165 - Temporal indication of cannabis use by means of thc glucuronide determination.
22326175 - Molecular methods for diagnosis of odontogenic infections.
8204415 - Diagnosis and monitoring of disseminated candidiasis based on serum/urine d/l-arabinito...
10445485 - The elimination profiles of tenoxicam and hydroxytenoxicam in equine urine and serum af...
22357505 - Biomedical mass spectrometry in today's and tomorrow's clinical microbiology laboratories.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-21
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  39     ISSN:  1521-009X     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-22     Completed Date:  2012-04-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2355-60     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Washington State University, Pullman, WA 99164-4630, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Chromatography, Liquid / methods*
Hydroxylation
Magnetic Resonance Spectroscopy
Mass Spectrometry / methods*
Methylation
Grant Support
ID/Acronym/Agency:
GM84546/GM/NIGMS NIH HHS
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Absorption and Metabolism of Chlorogenic Acids in Cultured Gastric Epithelial Monolayers.
Next Document:  Raloxifene glucuronidation in human intestine, kidney, and liver microsomes and in human liver micro...