Metabolic stability plays an important role in the success of drug candidates. An integrated high throughput microsomal stability assay was implemented using LC/MS/MS in our laboratory. We have applied this system to the routine metabolic screening of Wyeth compounds. In support of medicinal chemistry effort, we utilized this system to screen metabolic stability using different animal species (rat, mouse, human) and determine the potential difference in metabolic rate due to chirality. The system is also modified for cytochrome P450 phenotyping to identify which human CYP450 enzyme(s) is involved in the metabolic transformation of some compounds.
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