1. Optimized LC–ESI-ion trap MS to determine simultaneously isocorynoxeine and its phase I and II metabolites in rats with application to pharmacokinetics and mass balance investigation.
- Author
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Wang, Wei, Li, Bo, Chen, Ya Ping, Li, Mei Hong, and Hattori, Masao
- Subjects
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OXINDOLE alkaloids , *BIOACTIVE compounds , *METABOLITES , *PHARMACOKINETICS , *LABORATORY rats , *LIQUID chromatography-mass spectrometry - Abstract
Isocorynoxeine (ICOR) is one of the bioactive oxindole alkaloids inUncariaspecies. This study presents the pharmacokinetics and mass balance of ICOR in rats after oral dose of 40.0 mg/kg and intravenous dose of 4.0 mg/kg through detection of ICOR and its in vivo metabolites, using an optimized LC-MS with recoveries ranged from 94 to 104%, accuracy varied from 96 to 103%, and relative standard deviation for assay being less than 5%. ICOR reached its Cmaxof 336.7 ng/mL in plasma 3 hr after oral dose. The phase I metabolites of ICOR, 11-hydroxyisocorynoxeine (M1), and 10-hydroxyisocorynoxeine (M2) were detected in rat heart, kidneys, urine, and feces; whereas, in rat liver and bile, M1, M2, along with phase II metabolites, 11-hydroxyisocorynoxeine 11-O-β-D-glucuronide, and 10-hydroxyisocorynoxeine 10-O-β-D-glucuronide were identified. ICOR (77.0%) was excreted into feces and urine after oral administration within 72 hr, 0.93% drained into bile in 8 hr, 17.9% biotransformed into M1 and M2 at a ratio ofca. 1:1, and 0.028% detected in main organs attmax, in which brain uptake index is 3.2 ng/g. This work affords a developed and validated LC-MS for simultaneous determination of ICOR and itsin vivometabolites with improved precision and accuracy. [ABSTRACT FROM PUBLISHER]
- Published
- 2016
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