LC–MS/MS bioanalysis of plasma 1, 14-tetradecanedioic acid and 1, 16-hexadecanedioic acid as candidate biomarkers for organic anion-transporting polypeptide mediated drug–drug interactions. (13th September 2018)

• Record Type: Journal Article
• Authors: Santockyte, Rasa; Kandoussi, Hamza; Chen, Weiqi; Zheng, Naiyu; Venkatarangan, Lata; Gan, Jinping; Shen, Hong; Bonacorsi, Samuel J; Easter, John; Burrell, Richard; Zhang, Yan J; Zeng, Jianing
• Is Part Of: Bioanalysis. Volume 10:Number 18(2018)
• Page Start: 1473
• Page End: 1485
• Publication Date: 2018-09-13
• Subjects: 1, 14-tetradecanedioic acid -- 1, 16-hexadecanedioic acid -- DDI -- HDA -- TDA -- drug–drug interactions -- endogenous biomarker -- LC–MS/MS -- OATP -- organic anion-transporting polypeptides; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2018-0170
• Languages: English
• ISSNs: 1757-6180

Abstract

Aim: A robust LC–MS/MS assay was developed to quantify endogenous 1, 14-tetradecanedioic acid (TDA) and 1, 16-hexadecanedioic acid (HDA) in human plasma as potential biomarkers for evaluating drug–drug interactions mediated by the hepatic drug transporters, organic anion-transporting polypeptides.Results: This assay was validated using fit-for-purpose approach over standard curve range of 2.5–1000 nM for TDA and HDA using analyte-free charcoal-stripped human plasma as the surrogate matrix. Chromatographic separation condition was successfully optimized to separate TDA from an interference peak while maintaining both analytes in neutral forms to minimize carryover issue.Conclusion: The described assay is currently applied to a clinical study for evaluating TDA/HDA as potential substitute biomarkers for drug–drug interaction studies.