A Novel Hydrophilic Interaction Chromatography Assay Characterization of 4-Pyridoxic Acid, an Emergent Renal Organic Anion Transporter 1/3 Transporter Biomarker

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 areneeded to support the proposal. Materials & methods: A hydrophilic interaction chromatography (HILIC)–LC/MS/MSassay 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.

Keywords:

• 4-pyridoxic acid (PDA)
• biomarkers
• characterization
• HILIC
• OAT1/3

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/bio-2021-0110

Acknowledgments

The authors gracefully acknowledge department colleagues for helpful suggestions and guidance.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate Institutional Review Board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2144/000112170