A novel LC-MS/MS method for simultaneous estimation of obeticholic acid, glyco-obeticholic acid, tauro-obeticholic acid in human plasma and its application to a pharmacokinetic study.
human plasma
mass spectrometry
metabolites
obeticholic acid
pharmacokinetics
Journal
Journal of separation science
ISSN: 1615-9314
Titre abrégé: J Sep Sci
Pays: Germany
ID NLM: 101088554
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
revised:
24
12
2020
received:
06
10
2020
accepted:
30
12
2020
pubmed:
5
1
2021
medline:
26
10
2021
entrez:
4
1
2021
Statut:
ppublish
Résumé
A rapid, robust, simple, selective, and sensitive liquid chromatography-tandem mass spectrometry method was developed for the simultaneous estimation of obeticholic acid and its two pharmacologically active metabolites, glyco-obeticholic acid, and tauro-obeticholic acid in human plasma. The analytes and their heavy stable isotope-labeled internal standards were extracted from 250 μL human plasma by a solid-phase extraction technique. The method linearity was established over a concentration range of 0.410 to 120.466 ng/mL for obeticholic acid, 0.414 to 121.708 ng/mL for glyco-obeticholic acid, and 0.255 to 75.101 ng/mL for tauro-obeticholic acid. The method was fully validated as per current guidelines on bioanalytical method validation of "United States of Food and Drug Administration" and "European Medicines Agency." The method was successfully applied to study the pharmacokinetics of obeticholic acid, glyco-obeticholic acid, and tauro-obeticholic acid following oral administration of obeticholic acid tablets to healthy male volunteers. All the measured concentrations were within calibration curve ranges.
Identifiants
pubmed: 33395497
doi: 10.1002/jssc.202001050
doi:
Substances chimiques
obeticholic acid
0462Z4S4OZ
Chenodeoxycholic Acid
0GEI24LG0J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1307-1323Informations de copyright
© 2021 Wiley-VCH GmbH.
Références
Robert S. B. J., Use of obeticholic acid in patients with primary biliary cholangitis. Gastroenterol Hepatol. 2018;14:654-657.
David E. J. J., Obeticholic acid for the treatment of primary biliary cirrhosis. Expert Rev Gastroenterol Hepatol. 2016;10:1091-1099.
Ludovico A., Tetyana F., Luigi B., Olena T., Nazarii K., Obeticholic acid: A new era in the treatment of nonalcoholic fatty liver disease. Pharmaceuticals. 2018;11:104.
Thomas H., Therapy: Obeticholic acid for PBC. Nat Rev Gastroenterol Hepatol. 2016;13:558-559.
Christopher L. B., Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: Clinical utility and patient selection. Hepat Med. 2016;8:89-95.
Zhang R. Y., Gu Y., Zhang A., Dong S. Q., Li Q. S., Wei G. L., Si D. Y., Determination of obeticholic acid in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acta Pharm Sin. 2018;53:292-301.
Li X. Y., Zhu S. H., Yang F., Hu G. X., Yuan L. J., An ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of obeticholic acid in rat plasma and its application in preclinical pharmacokinetic studies. J Chromatogr B. 2019;1121:82-88.
Roda A., Aldini R., Camborata C., Spinozzi S., Franco P., Cont M., D'Errico A., Vasuri F., Degiovanni A., Maroni L., Adorini L., Metabolic profile of obeticholic acid and endogenous bile acids in rats with decompensated liver cirrhosis. Clin Transl Sci. 2017;10:292-301.
Edwards J. E., LaCerte C., Peyret T., Gosselin N. H., Marier J. F., Hofmann A. F., Shapiro D, Modeling and experimental studies of obeticholic acid exposure and the impact of cirrhosis stage. Clin Transl Sci. 2016;9:328-336.