Determination of the endogenous OATP1B biomarkers glycochenodeoxycholate-3-sulfate and chenodeoxycholate-24-glucuronide in human and mouse plasma by a validated UHPLC-MS/MS method

Yan Jin, Yang Li, Eric D. Eisenmann, William D. Figg, Sharyn D. Baker, Alex Sparreboom, Shuiying Hu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Glycochenodeoxycholate-3-sulfate (GCDCA-S) and chenodeoxycholate-24-glucuronide (CDCA-24G) are bile acid metabolites that potentially serve as endogenous biomarkers for drug-drug interactions mediated by the hepatic uptake transporters OATP1B1 and OATP1B3. We developed and validated a novel UHPLC-MS/MS method for the quantitative determination of GCDCA-S and CDCA-24G in mouse and human plasma with a lower limit of quantitation of 0.5 ng/mL. Chromatographic separation was achieved on an Accucore aQ column (50 mm × 2.1 mm, dp = 2.6 μm) maintained at 20 °C and a gradient mobile phase comprising 2 mM ammonium acetate in water and methanol. The extraction recoveries of GCDCA-S and CDCA-24G were >80 %, and linear (r2 > 0.99) calibration curves ranged 0.5–100 ng/mL (CDCA-24G and GCDCA-S in mouse plasma) or 0.5–1000 ng/mL (GCDCA-S in mouse plasma). Values for precision (CV < 11.6 %) and accuracy bias (10.9 %) of analyte-spiked quality control samples verified that water was an acceptable matrix to prepare calibrators. This method was successfully applied to establish baseline activity of OATP1B1/OATP1B3 in humans and mice and establish the in vivo effects of OATP1B1/OATP1B3 inhibitors rifampin and micafungin.

Original languageEnglish
Article number123437
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1210
DOIs
StatePublished - 1 Nov 2022
Externally publishedYes

Keywords

  • Bile acids
  • Drug-drug interactions
  • Endogenous biomarkers
  • OATP1B transport
  • UHPLC-MS/MS

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