Abstract
The disposition and metabolism of hydrastine was investigated in 11 healthy subjects following oral dose of 2.7 g of Goldenseal supplement containing 78 mg hydrastine. Serial blood samples were collected for 48 h and urine was collected for 24 h. Hydrastine serum and urine concentrations were determined by LC-MS/MS. Pharmacokinetic parameters for hydrastine were calculated using non-compartmental methods. Maximal serum concentration (Cmax) was 225 ± 100 ng/ml, Tmax was 1.5 ± 0.3 h, and AUC was 6.4 ± 4.1 ng*h/ml*kg. The elimination half-life was 4.8 ± 1.4 h. Metabolites of hydrastine were identified in serum and urine by using liquid chromatography coupled to high-resolution mass spectrometry (LC-QToF). Hydrastine metabolites were identified by various mass spectrometric techniques such as accurate mass measurement, neutral loss scanning and product ion scanning using Q-ToF and triple quadrupole instruments. The identity of phase II metabolites was further confirmed by hydrolysis of glucuronide and sulfate conjugates using bovine β-glucuronidase and Helix Pomatia sulfatase/glucuronidase enzyme preparation. Hydrastine was found to undergo rapid and extensive phase I and phase II metabolism. Reduction, O-demethylation, N-demethylation, hydroxylation, aromatization, lactone hydrolysis and dehydrogenation of alcohol group formed by lactone hydrolysis to ketone group were observed during phase I biotransformation of hydrastine. Phase II metabolites were primarily glucuronide and sulfate conjugates. Hydrastine undergoes extensive biotransformation, and some metabolites may have pharmacological activity; further study is needed in this area.
- HPLC
- mass spectrometry/MS
- metabolite disposition
- metabolite identification
- natural products
- pharmacokinetics
- The American Society for Pharmacology and Experimental Therapeutics