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- Title
Determination of (-)-epigallocatechin-3-gallate octaacetate and its metabolites in plasma of rats for pharmacokinetic study by ultra-performanceliquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry.
- Authors
Kai On Chu; Gene Chi Wai Man; Sze Wan Hung; Tak Hang Chan; Wai Yip Thomas Lee; Kwok Ping Chan; Chi Pui Pang; Chi Chiu Wang
- Abstract
(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exactmassmethod with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01-2.5 µg/mL were within acceptable limits. The sensitivitywas improved by 25 folds using pro-EGCGammoniumadduct [M + NH4]+. This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 µg/mL, time-ofmaximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr-1. The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites.
- Subjects
EPIGALLOCATECHIN gallate; ORAL drug administration; METABOLITES; PHARMACOKINETICS; FORMIC acid; COLUMNS
- Publication
Frontiers in Pharmacology, 2022, Vol 13, p1
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2022.1025053