Affiliation:
1. Drug Metabolism, Gilead Sciences Inc., Foster City, CA 94404, USA
Abstract
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.
Subject
Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry
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