As our understanding of cytochrome P450-mediated metabolism grows and chemical design is able to effectively modulate P450 clearance, our attention turns to other metabolising enzymes and their potential impact on clinical efficacy and safety.  Notably, aldehyde oxidase (AO) and xanthine oxidase (XO) may be potentially important contributors to drug clearance, particularly in certain areas of chemical space.  This work describes an investigation of the metabolism of precedented AO and XO substrates in a range of matrices.