Multiple surface plasmon biosensor assay as new tool for probing metabolic evaluation of CYP2D6

The determination of candidate drug metabolism is a vital stage in drug development in the pharmaceutical industry. In our previous investigation, a surface plasmon biosensor has been developed with self-assembly monolayer immobilised microsomes containing CYP1A2, NADPH reductase and Cytochrome b5. The basis of the methodology was proven using NADPH, which allows enzyme to complete the catalytic cycle, rather than simply evaluate association and dissociation constants. The purpose of this investigation is to demonstrate the capacity of the sensor to be used with CYP2D6 microsomes and define drug–drug interactions, pseudo-catalytic rate, identify unreactive substrates and inhibition using a range of substrates. By demonstrating differentiation between each of these conditions, it is possible to suggest that this sensor offers a complete alternative to the present LC–MS and fluorescent methods utilised for metabolism assay investigations. The assay method is now proven to be suitable for trialling against potential candidate drugs.