Implementation of a novel ultra fast metabolic stability analysis method using exact mass TOF-MS

Bioanalysis. 2017 Feb;9(4):359-368. doi: 10.4155/bio-2016-0187. Epub 2017 Jan 11.

Abstract

Aim: Increasing numbers of compounds requiring stability data means highly optimized methods capable of rapid turnaround are desirable during early discovery. Materials and methods/results: An advanced, generic analytical workflow for metabolic stability has been developed that utilizing ballistic gradient LC (sub 1 min run times), exact mass TOF-MS (Waters Xevo-G2-XS Q-TOF) and automated data processing (Waters UNIFI software) allowed for rapid integration and interpretation of all data produced, eliminating the need for method development and manual processing. We can analyze and process 96 compounds across two species in quadruplicate in a 24-h period with no method development.

Conclusion: An advanced bioanalytical workflow has increased our capacity threefold and reduced our instrument/processing needs threefold.

Keywords: automated data; automation; ballistic gradient; discovery processing; efficiency; high resolution; mass spectrometry; metabolic stability.

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical / methods*
  • Chromatography, High Pressure Liquid
  • Drug Discovery
  • Electronic Data Processing
  • Humans
  • Liver / metabolism
  • Mass Spectrometry / methods*
  • Molecular Weight
  • Rats
  • Reproducibility of Results
  • Software
  • Tandem Mass Spectrometry
  • Technology, Pharmaceutical
  • Workflow