Detection of an Endogenous Urinary Biomarker Associated With CYP2D6 Activity Using Global Metabolomics

Jessica Tay-Sontheimer; Laura M Shireman; Richard P Beyer; Taurence Senn; Daniela Witten; Robin E Pearce; Andrea Gaedigk; Cletus L Gana Fomban; Justin D Lutz; Nina Isoherranen; Kenneth E Thummel; Oliver Fiehn; J Steven Leeder; Yvonne S Lin


Pharmacogenomics. 2014;15(16):1947-1962. 

In This Article


In conclusion, we demonstrated that discovery of human biomarkers of CYP2D6 can be facilitated using a global metabolomics approach. We found that a positive ion with m/z of 444.3102 was associated with the urinary DM/DX ratio, an established method of CYP2D6 phenotyping, in two cohorts of children and was altered following CYP2D6 inhibition in adults. The ability of this ion to distinguish between CYP2D6 metabolizer phenotypes is currently limited to PM and non-PM phenotypes. Clearly, future structural identification of M1 and its parent are needed and may lead to a combined marker of CYP2D6 phenotype that may be more sensitive than the metabolite alone.