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    
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.
Upendra P Dahal; Jeffrey P Jones; John A Davis; Dan A Rock
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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    
Department of Chemistry, Washington State University, Pullman, WA 99164-4630, USA.
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MeSH Terms
Chromatography, Liquid / methods*
Magnetic Resonance Spectroscopy
Mass Spectrometry / methods*
Grant Support

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

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