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Scientific article
English

The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites

Contributors

Staack, Roland F.; Varesio, Emmanuel; Hopfgartner, Gerard

Published in

RCM. Rapid communications in mass spectrometry, vol. 19, no. 5, p. 618-626

Publication date

2005

Abstract

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.

Keywords

  • Animals
  • 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
  • Pharmacokinetics
  • Propanolamines/administration & dosage/pharmacokinetics
  • Rats
  • Spectrometry, Mass, Electrospray Ionization/instrumentation/methods
  • Systems Integration

UNIGE affiliation entities

Citation (ISO format)

STAACK, Roland F., VARESIO, Emmanuel, HOPFGARTNER, Gerard. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites. In: RCM. Rapid communications in mass spectrometry, 2005, vol. 19, n° 5, p. 618–626. doi: 10.1002/rcm.1829

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

0951-4198
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Technical informations

Creation

20/07/2009 14:51:00

First validation

20/07/2009 14:51:00

Update

14/03/2023 15:10:19

Status update

14/03/2023 15:10:19

Last indexation

29/10/2024 11:52:26
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