Development and validation of an LC-MS/MS method to quantify kynurenic acid in human plasma.

Background: Monitoring levels of endogenous biomarkers has become an alternative approach to assess transporter-mediated drug-drug interactions in clinical trials. Among the biomarkers of interest, kynurenic acid is effective for the human organic anion transporters OAT1 and OAT3. Here, a simple and robust bioanalytical method was developed using LC-MS/MS to quantify kynurenic acid in human plasma. Results: This method achieved a LLOQ of 10 nm with acceptable signal-to-noise ratio (S/N >5). In addition, an interfering agent, tryptophan, was identified and separated chromatographically. A full method validation was performed in the spirit of GLP. Conclusion: This method can serve as a tool readily available to assess potential drug-drug interactions mediated by inhibition of OAT1 and OAT3 activities.