Pharmacokinetics and metabolism of GW9508 in rat by liquid chromatography/electrospray ionization tandem mass spectrometry
In: Journal of Pharmaceutical and Biomedical Analysis, Jg. 170 (2019-06-01), S. 176-186
Online
unknown
Zugriff:
In this study, a simple, fast and sensitive LC/MS/MS method was developed and validated for the determination of GW9508 in rat plasma. The sample was precipitated with acetonitrile and subsequently separated on ZORBAX Eclipse XDB C18 column (50 mm × 2.1 mm, 5 μm). Mobile phase was composed of 0.1% formic acid in water and acetonitrile with gradient elution, at a flow rate of 0.4 mL/min. The analyte and internal standard were quantitatively monitored with precursor-to-product transitions of m/z 348.2→183.1 and m/z 397.2→260.2, respectively. The linearity of the assay was evident in the range of 1–1000 ng/mL with correlation coefficient more than 0.998. The validation parameters were all within the acceptable limits. The validated method has been successfully applied to the pharmacokinetics study of GW9508 in rat plasma, and our results demonstrated that GW9508 showed low clearance, moderate half-life and ideal bioavailability (54.88%). Furthermore, metabolites stemmed from rat plasma, rat hepatocytes and human hepatocytes were analyzed by an LC-Q-Exactive-Orbitrap-MS assay, resulting in the identification of seven metabolites based on the accurate mass and fragment ions. Acylglucuronide conjugate (M6) was found as the most abundant metabolite in all tested matrices. The metabolic pathways were proposed as hydroxylation and glucuronidation. This study provided an overview of disposition of GW9508, which is highly instructive for better understanding the effectiveness and toxicity of this drug.
Titel: |
Pharmacokinetics and metabolism of GW9508 in rat by liquid chromatography/electrospray ionization tandem mass spectrometry
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Autor/in / Beteiligte Person: | Wu, Qiuhong ; Li, Yu ; Yang, Xue ; Zhang, Hui |
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Zeitschrift: | Journal of Pharmaceutical and Biomedical Analysis, Jg. 170 (2019-06-01), S. 176-186 |
Veröffentlichung: | Elsevier BV, 2019 |
Medientyp: | unknown |
ISSN: | 0731-7085 (print) |
DOI: | 10.1016/j.jpba.2019.03.040 |
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