Document Detail

The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites.
MedLine Citation:
PMID:  15685686     Owner:  NLM     Status:  MEDLINE    
An approach has been developed for drug metabolism studies of non-radiolabeled compounds using on-line liquid chromatography/tandem mass spectrometry (LC/MS/MS) combined with chip-based infusion following fraction collection. The potential of this approach, which improves the data quality compared with only LC/MS analysis, has been investigated for the analysis of in vitro metabolites of tolcapone and talinolol, two compounds with well-characterized metabolism. The information-dependent LC/MS/MS analysis enables the characterization of the major metabolites while the chip-based infusion is used to obtain good product ion spectra for lower level metabolites, to generate complementary MS information on potential metabolites detected in the LC/MS trace, or to screen for unexpected metabolites. Fractions from the chromatographic analysis are collected in 20 second steps, into a 96-well plate. The fractions of interest can be re-analyzed with chip-based infusion on a variety of mass spectrometers including triple quadrupole linear ion trap (QqLIT or Q TRAP) and QqTOF systems. Acquiring data for several minutes using multi-channel acquisition (MCA), or signal averaging while infusing the fractions at approximately 200 nL/min, permits about a 50 times gain in sensitivity (signal-to-noise) in MS/MS mode. A 5-10 microL sample fraction can be infused for more than 30 min allowing the time to perform various MS experiments such as MS(n), precursor ion or neutral loss scans and accurate mass measurement, all in either positive or negative mode. Through fraction collection and infusion, a significant gain in data quality is obtained along with a time-saving benefit, because the original sample needs neither to be re-analyzed by re-injection nor to be pre-concentrated. Therefore, a novel hydroxylated talinolol metabolite could be characterized with only one injection.
Roland F Staack; Emmanuel Varesio; Gérard Hopfgartner
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Rapid communications in mass spectrometry : RCM     Volume:  19     ISSN:  0951-4198     ISO Abbreviation:  Rapid Commun. Mass Spectrom.     Publication Date:  2005  
Date Detail:
Created Date:  2005-02-17     Completed Date:  2005-05-16     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  8802365     Medline TA:  Rapid Commun Mass Spectrom     Country:  England    
Other Details:
Languages:  eng     Pagination:  618-26     Citation Subset:  IM    
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MeSH Terms
Benzophenones / administration & dosage,  pharmacokinetics*
Cells, Cultured
Chromatography, High Pressure Liquid / methods*
Equipment Design
Equipment Failure Analysis
Flow Injection Analysis / instrumentation*,  methods
Metabolic Detoxication, Drug / physiology
Microfluidic Analytical Techniques / instrumentation*,  methods
Microsomes, Liver / drug effects,  metabolism*
Nitrophenols / administration & dosage,  pharmacokinetics*
Online Systems
Propanolamines / administration & dosage,  pharmacokinetics*
Spectrometry, Mass, Electrospray Ionization / instrumentation*,  methods
Systems Integration
Reg. No./Substance:
0/Benzophenones; 0/Nitrophenols; 0/Propanolamines; 3S82268BKG/talinolol; CIF6334OLY/tolcapone

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

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