A computer program for automated data evaluation to support in vitro higher-throughput screening for drug metabolism and pharmacokinetics attributes

Rapid Commun Mass Spectrom. 2004;18(18):2046-52. doi: 10.1002/rcm.1581.

Abstract

With the advances in analytical techniques, higher-throughput screening for drug metabolism and pharmacokinetics (DMPK) attributes has become an integral part of drug discovery. However, as the number of compounds increases, the volume of data that needs to be processed and evaluated increases exponentially. As a result, a major challenge for the analytical chemist is how to quickly process the vast amount of data so as to keep up with the throughput of the screening assay. We have developed a customized computer program for automated evaluation of the liquid chromatography/tandem mass spectrometric (LC/MS/MS) data generated from the in vitro DMPK screening assays. This program performs automatic data processing and quality control. It identifies analytical anomalies, such as low internal standard intensity and poor reproducibility of replicates. All analytical anomalies for individual compounds are summarized into an 'E-Log' in a color-coded format for reviewing. With the use of this program and other supporting software, data processing and evaluation for up to 100 compounds are accomplished in several minutes.

Publication types

  • Comparative Study
  • Evaluation Study
  • Validation Study

MeSH terms

  • Algorithms*
  • Animals
  • Automation / methods
  • Blood-Brain Barrier / metabolism*
  • Calibration
  • Capillaries / metabolism
  • Cattle
  • Cells, Cultured
  • Endothelium, Vascular / metabolism
  • In Vitro Techniques
  • Pharmaceutical Preparations / analysis*
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Software*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • User-Computer Interface

Substances

  • Pharmaceutical Preparations