Metabolic Interspecies Comparison Using LC/MS and Principle Component Analysis

摘要

LC/MS(/MS) has long been a powerful technique for metabolism studies in drug discovery. In interspecies metabolite comparisons, it is necessary to compare data from multiple species across several time points to determine the most similar species analog for future studies. Data from these experiments is often vast and complex. Use of principle component analysis (PCA) simplifies data analysis by allowing comparison of all data in a single, multivariate analysis. Buspirone was incubated using rat, dog, monkey and human hepatocytes. The data was processed using MarkerView~(TM) PCA Software. This software analyzes MS data to group the samples according to their similarities and differences. Human metabolism of buspirone was most similar to metabolism in monkeys and rats showed the most different metabolic trends. MS/MS data were analyzed to identify and confirm the metabolites responsible for the similarities and differences. By using PCA for interspecies metabolism comparison, it was possible to process the entire set of a data as a single set and obtain results. Through simultaneous processing of this large data set, data analysis was greatly simplified compared to the traditional workflow of comparing a single time point and control pair. PCA successfully determined groupings of the species, as well as metabolic trends.