UHPLC–MS/MS Bioanalysis of Human Plasma Coproporphyrins as Potential Biomarkers for Organic Anion-Transporting Polypeptide-Mediated Drug Interactions

Abstract

Aim: Coproporphyrins (CP-I and CP-III) have been identified as possible biomarkers to predict human hepatic organic anion-transporting polypeptides-mediated-drug-interactions for a new drug entering clinical development. Results: The method is applicable to quantify plasma CP-I and CP-III within 0.078–15.0 nM. The results identify and address a number of challenges encountered with porphyrin assays such as photodegradation and interferences. To overcome interferences from ubiquitous porphyrins, a surrogate matrix was used to prepare calibration standards. Quality controls were prepared in plasma and surrogate matrix to ensure parallelism between surrogate matrix and plasma. Conclusion: A robust UHPLC–MS/MS assay was developed and validated for CP-I and CP-III in plasma, and is currently applied to clinical studies to confirm suitability of Coproporphyrins as a potential substitute for drug–drug interaction study.

Keywords::

• coproporphyrin I
• CP-I
• coproporphyrin III
• CP-III
• DDI
• drug–drug interactions
• endogenous biomarker
• human hepatic organic anion-transporting polypeptides
• human plasma
• OATP
• UHPLC–MS/MS

Acknowledgements

The authors would like to express their gratitude to W Humphreys and J Gan for their guidance and continuous input throughout the course of the clinical studies.

Financial & competing interests disclosure

H Kandoussi, R Santockyte, J Zeng, H Shen, J Gan, W Chen, R Languish, P Shipkova, J Easter, S Bonacorsi, P Kadiyala, P Marathe, Y Zhang and R Pillutla are current employees of Bristol-Myers Squibb Company (BMS). L Yurong is a current employee of Gilead. K Shah, T Mariannino and P Paterson are employees of PPD. All financial support for the studies reported herein was provided by BMS. The authors have no other 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 apart from those disclosed.

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: www.tandfonline.com/doi/suppl/10.2144/000112170