Accelerated throughput metabolic route screening in early drug discovery using high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis
The resource investment required to characterise the metabolic fate of a compound is relatively large, meaning that within a drug discovery environment relatively few compounds are characterised in depth. Rate‐limiting steps include the setting up of a complex array of mass spectrometry experiments...
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| Veröffentlicht in: | Rapid communications in mass spectrometry 2005-01, Vol.19 (18), p.2659-2670 |
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| container_title | Rapid communications in mass spectrometry |
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| creator | Mortishire-Smith, Russell J. O'Connor, Desmond Castro-Perez, Jose M. Kirby, Jane |
| description | The resource investment required to characterise the metabolic fate of a compound is relatively large, meaning that within a drug discovery environment relatively few compounds are characterised in depth. Rate‐limiting steps include the setting up of a complex array of mass spectrometry experiments and the subsequent analysis of the large data sets produced. We describe here a strategy for the evaluation of metabolic routes using full‐scan high‐resolution liquid chromatography/quadrupole time‐of‐flight mass spectrometry (LC/QToFMS) with automated data analysis using Metabolynx™, a commercially available software package. Data from several structurally diverse compounds taken from the literature illustrate that, with careful setting of key parameters, this approach is able to indicate the presence of a wide range of metabolites with only a limited requirement for manual intervention. Copyright © 2005 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/rcm.2111 |
| format | Article |
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| ispartof | Rapid communications in mass spectrometry, 2005-01, Vol.19 (18), p.2659-2670 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals Automation Chromatography, Liquid Diazepam - chemistry Diazepam - metabolism Drug Evaluation, Preclinical - methods Indinavir - chemistry Indinavir - metabolism Mass Spectrometry Microsomes, Liver - metabolism Molecular Structure Pharmaceutical Preparations - chemistry Pharmaceutical Preparations - metabolism Rats Reference Standards Sensitivity and Specificity Time Factors |
| title | Accelerated throughput metabolic route screening in early drug discovery using high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis |
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