Automated metabolite identification process

R. Ramanathan, D.L. McKenzie, M. Tugnait, K. Siebenaler, Application of semi-automated metabolite identification software in the drug discovery process for rapid identification of metabolites and the cytochrome P450 enzymes responsible for theirformation, J. Pharm. Biomed. Anal., 28 (2002) 945. 

A QTRAP instrument provides a wide range of options and greater power for metabolite identification. One aspect, which can often be a struggle, is the ability to automate much of this analysis for increased throughput, especially as metabolite identification is moved to earlier stages of the dmg discovery process. Recent work... 

Rourick, R. A., Jenkins, K. M., Walsh, J. P., Xu, R., Cai, Z., and Kassel, D. B. (2002). Integration of custom LC/MS automated data processing strategies for the rapid assessment of metabolic stability and metabolite identification in drug discovery. In Proceedings of the 50th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL. 

Isotopic cluster analysis can be built into the automated processing method and is used to target potential metabolites with the desired isotope ratios (Kind and Fiehn, 2006). For example, chlorine or bromine or radiolabeled drugs/metabolites can be pinpointed, at low levels, within a complex matrix background to dramatically enhance specificity and increase confidence in metabolite identification (Jindal and Lutz, 1986 Shirley et al., 1997). 

The analysis of phytochemicals is a tedious process involving several steps in which care must be taken to avoid degradation and contamination. Recent advancements in extraction, concentration, purification and analytical procedures of phytochemicals have been made, but additional developments are needed to assist in the identification and quantification of the diverse array of phytochemicals present in plants and foods, as well as metabolites in biological samples. Specifically there is a need to automate sample extraction, clean-up, and concentration steps to facilitate the screening of phytochemicals develop analytical methods with improved sensitivity, resolution and throughput that utilize less organic solvents and develop concentration and purification methods to produce analytical standards that are not available commercially. Continued advancements in sample preparation and analytical techniques will assist researchers in their quest to identify and quantify the vast array of phytochemicals present in plants... 

Instrument advances in recent years have led to an everincreasing quantity of data that require examination. The automated identification of metabolites and their structures will be crucial to the success of biotransformation studies in drug discovery. Several software packages have been developed that accelerate various stages of this process. One such program is Metabolite ID 1.4 for Analyst from Applied Biosystems/MDS Sciex. Other instrument vendors offer similar software packages to help in metabolite structure elucidation. Metabolite ID 1.4 for Analyst will acquire full-scan chromatographic data of... 

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