Amperometric enzyme biosensors for the analysis of drugs and metabolites

Amperometric enzyme biosensors have considerable potential for continuous monitoring of drugs or metabolites in biological fluids. One can envisage a time when the release of a potent drug could be controlled by a microprocessor, in response to information fed back from a biosensor, though there are many technological challenges to be overcome before this becomes a reality. Glucose sensors, based on oxidation of the analyte by glucose oxidase, have been commercially available for ex vivo use for some time, but the use of analogous technology for assay of drugs and other biomolecules is more problematic and has been slow to develop. This review considers the advances in immobilization technology and electron transfer mediation which are needed to enlarge the number of analytes for which biosensors can be developed. Many design strategies have been investigated using glucose oxidase, and their advantages and limitations are discussed. With a view to the future, advances in the use of microbial enzymes such as reductases are considered. Microbial reductases-are known to metabolise drugs but often are complicated by the need for soluble coenzymes such as NADH or NADPH. Attempts have been made to create warfarin sensors using microbial enzymes and this serves as a paradigm for other pharmaceutical analytes. Novel transfer mediators based on rhodium are an exciting development which may make possible the use of reductases in sensors, opening out the field to a variety of new analytes.