UHPLC–MS/MS bioanalysis of human plasma coproporphyrins as potential biomarkers for organic anion-transporting polypeptide-mediated drug interactions. (11th May 2018)

• Record Type: Journal Article
• Authors: Kandoussi, Hamza; Zeng, Jianing; Shah, Kumar; Paterson, Patricia; Santockyte, Rasa; Kadiyala, Pathanjali; Shen, Hong; Shipkova, Petia; Langish, Robert; Burrrell, Richard; Easter, John; Mariannino, Thomas; Marathe, Punit; Lai, Yurong; Zhang, Yan; Pillutla, Renuka
• Is Part Of: Bioanalysis. Volume 10:Number 9(2018)
• Page Start: 633
• Page End: 644
• Publication Date: 2018-05-11
• Subjects: 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; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2017-0246
• Languages: English
• ISSNs: 1757-6180

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.