Simultaneous determination of SU5416 and its phase I and phase II metabolites in rat and dog plasma by LC/MS/MS |
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Authors: | Zhao Y Yang C Y Haznedar J Antonian L |
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Institution: | Department of Bioanalysis and Pharmacokinetics, SUGEN Inc., 230 E. Grand Avenue, South San Francisco, CA 94080, USA |
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Abstract: | SU5416, Z-3-(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a cytostatic substance in development as an anti-angiogenic agent. SU5416 has several phase I and phase II metabolites including SU9838, SU6595, SU6689, 5′-hydroxy glucuronide of SU5416 and 5′-acyl glucuronide of SU5416. In order to support the preclinical studies, a liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method for simultaneous determination of SU5416 and its metabolites in rat and dog plasma was developed. This method is fast, simple, sensitive (LOQ=2.0 ng/ml), reproducible and has a wide linear range (2.0–5000 ng/ml for SU5416, 2.0–2000 ng/ml for SU6689 and 2.0–1000 ng/ml for SU9838 and SU6595). This method was applied to rat and dog plasma samples obtained from pharmacokinetic and toxicokinetic studies. |
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Keywords: | SU5416 Drug analysis Liquid chromatography Mass spectrometry LC/MS/MS |
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