A high throughput CYP450 cocktail IC50 assay has been developed recently by the DMPK and Analytical team of HDB

DMPK and Analytical team at HDB has recently developed a high throughput CYP450 cocktail IC50 assay to determine the potential of test agents to inhibit human CYP450 enzymes and/or other CYP450 enzymes from different species. The newly developed assay data will be very helpful to assess drug-drug interaction potential in human which is liable for many marketing drug withdrawals. The compounds will be diluted into 8 concentrations and then co-incubated respectively with cocktail of specific substrates of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. The ability of the test article to prevent the metabolism of the substrates can be determined. The substrates and control inhibitors used in this study are consistent with those recommended by the FDA. An LC-MS/MS method is developed to simultaneously detect the metabolites of seven substrates for six isoenzymes (two substrates are selected for CYP3A4).