A novel hydrophilic interaction chromatography assay characterization of 4-pyridoxic acid, an emergent renal organic anion transporter 1/3 transporter biomarker

Author:

Towner Justin1,Rago Brian1,Rodrigues David1,Vourvahis Manoli2,Holliman Chris1

Affiliation:

1. Pfizer Global Research & Development, Medicinal Sciences, Groton, CT 06340, USA

2. Pfizer Global Research & Development, Clinical Pharmacology, New York, NY, 10017, USA

Abstract

Aim: 4-pyridoxic acid (PDA) has been proposed as an endogenous biomarker for renal organic anion transporter 1/3 (OAT1/3) inhibition. Clinical data are needed to support the proposal. Materials & methods: A hydrophilic interaction chromatography (HILIC)–LC/MS/MS assay was developed and characterized to support clinical drug–drug interaction (DDI) studies. Results: A HILIC–LC/MS/MS assay was successfully developed. PDA was measured in two clinical DDI studies; one where no significant OAT1/3 inhibition was observed and a second where a known inhibitor of the transporter was dosed. In both clinical studies, PDA plasma concentrations correlate to OAT1/3 function. Conclusion: The analysis of study samples from two clinical DDI studies using a HILIC–LC/MS/MS assay contributes further evidence that PDA is an endogenous biomarker for OAT1/3 inhibition.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

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