Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2019
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.
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Li Xiang-Yu, Zhu Sheng-Hong, Yang Fang, Hu Guo-Xin, Yuan Ling-Jing
Аннотация
UNLABELLED: Currently, ursodeoxycholic acid (UDCA) is the only clear medical treatment for primary biliary cholangitis (PBC). However, approximately 40% of patients are not sensitive to UDCA. In recent years, obeticholic acid (OCA) combined with UDCA has been used in the PBC patients who were not sensitive to UDCA, or as monotherapy for PBC adult patients who are intolerant to UDCA.
OBJECTIVE: To develop and validate a specific, sensitive and reliable tandem mass spectrometry (UPLC-MS/MS) method for the determination of obeticholic acid (OCA) in rat plasma.
METHODS: Plasma samples were treated with liquid-liquid extraction. Diazepam was selected as the internal standard (IS). Chromatographic separation was achieved by an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) and a mobile phase consisting of acetonitrile and ultrapure water (containing 0.1% formic acid). The analyte was detected in positive ion mode by electrospray ionization mass spectrometry (ESI-MS). Multiple reaction monitoring (MRM) methods were used to detect specific precursor and product ions. The target ion pair of OCA was 419.38 → 401.22, and the IS was 285.05 → 193.02.
RESULTS: The linear range of OCA in rat plasma was 0.05-50 μg/mL (R2 = 0.992); the recovery rate was 91.34%-97.37%. This assay showed good intra- and inter-day precision and accuracy. No significant matrix effects in this study.
CONCLUSION: A specific, sensitive and reliable quantitative analysis method was established to detect OCA after oral/intravenous administration in rat plasma via UPLC-MS/MS. It was appropriate for preclinical pharmacokinetic studies of OCA.
OBJECTIVE: To develop and validate a specific, sensitive and reliable tandem mass spectrometry (UPLC-MS/MS) method for the determination of obeticholic acid (OCA) in rat plasma.
METHODS: Plasma samples were treated with liquid-liquid extraction. Diazepam was selected as the internal standard (IS). Chromatographic separation was achieved by an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) and a mobile phase consisting of acetonitrile and ultrapure water (containing 0.1% formic acid). The analyte was detected in positive ion mode by electrospray ionization mass spectrometry (ESI-MS). Multiple reaction monitoring (MRM) methods were used to detect specific precursor and product ions. The target ion pair of OCA was 419.38 → 401.22, and the IS was 285.05 → 193.02.
RESULTS: The linear range of OCA in rat plasma was 0.05-50 μg/mL (R2 = 0.992); the recovery rate was 91.34%-97.37%. This assay showed good intra- and inter-day precision and accuracy. No significant matrix effects in this study.
CONCLUSION: A specific, sensitive and reliable quantitative analysis method was established to detect OCA after oral/intravenous administration in rat plasma via UPLC-MS/MS. It was appropriate for preclinical pharmacokinetic studies of OCA.