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.

Autor: Jin Y; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Li Y; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Eisenmann ED; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Figg WD; Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA., Baker SD; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Sparreboom A; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA., Hu S; Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA; Division of Outcomes and Translational Sciences, College of Pharmacy, The Ohio State University, Columbus, OH, USA. Electronic address: hu.1333@osu.edu.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2022 Nov 01; Vol. 1210, pp. 123437. Date of Electronic Publication: 2022 Aug 27.
DOI: 10.1016/j.jchromb.2022.123437
Abstrakt: 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 (r 2  > 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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