A novel LC-MS approach for the detection of metabolites in DMPK studies

Bioanalysis. 2010 Oct;2(10):1767-78. doi: 10.4155/bio.10.115.

Abstract

Background: The profiling and quantification of drug metabolites in discovery and development bioanalysis studies is playing an increasingly important role in early candidate selection. Using a conventional tandem quadrupole mass spectrometer this activity normally requires several analytical runs to acquire the necessary analytical data.

Results: In this article we present the use of a new tandem quadrupole mass spectrometer equipped with a novel collision cell design, which allows the rapid switching between multiple reaction monitoring and full-scan MS mode. This approach allowed for the collection of multiple reaction monitoring data and full-scan data with no loss in sensitivity, with analysis times in the 1-2 min range.

Conclusion: A modified approach of using the multiple reaction monitoring data to trigger the acquisition of full scan MS/MS data is described, where the data is collected on the trailing edge of the LC-MS peak, thus improving data quality and throughput.

MeSH terms

  • Animals
  • Chromatography, Liquid / methods*
  • Drug Discovery
  • Glucuronides / analysis
  • Glucuronides / metabolism
  • Glucuronides / pharmacokinetics
  • Pharmaceutical Preparations / analysis*
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Propranolol / analysis
  • Propranolol / metabolism
  • Propranolol / pharmacokinetics
  • Rats
  • Tandem Mass Spectrometry / methods*

Substances

  • Glucuronides
  • Pharmaceutical Preparations
  • Propranolol