Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE:Astragali radix is one of the well-known traditional Chinese herbal medicine, and possesses various biological functions, such as hepatoprotective and anticancer. In present study, to investigate the metabolism and pharmacokinetics of the major constituents of A. radix, a sensitive ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-MS/MS) method with shorter chromatographic running time was developed and validated for simultaneous quantification of formononetin, ononin, calycosin, calycosin-7-β-glucoside, astragaloside IV and their glucuronide metabolites in rat plasma after oral administration of water extract of A. radix at two different doses. MATERIALS AND METHODS:The chromatographic separation was achieved on a C18 column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 0.3mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via electrospray ionization (ESI) source in positive ionization mode. Samples were pre-treated by a single-step protein precipitation with methanol, and erlotinib was used as internal standard (IS). RESULTS:The current UPLC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effects and stability. The lowest limit of quantifications (LLOQ) were 1ng/mL for all analytes. After oral administration, the plasma concentrations of the glucuronides, especially calycosin-3'-glucuronide, were much higher than the parent compounds. The mean half-life (t1/2) was between 1 and 5h, and the metabolites were eliminated faster than the parent constituents. The median (range) time to reach maximum plasma concentration (Tmax) was between 0.5 and 1h. CONCLUSIONS:This is the first study of the pharmacokinetic study of bioactive compounds and their glucuronides in male rat plasma after oral administration of water extract of A. radix. The results demonstrated the biotransformation between the bioactive isoflavonoids and their glucuronides was extensive in rats and provided a significant basis for better understanding the absorption and metabolism mechanism of A. radix. Furthermore, this study could suggest that future studies should focus on the metabolites and biotransformation between the bioactive constituents when conducting a drug efficacy study.
journal_name
J Ethnopharmacoljournal_title
Journal of ethnopharmacologyauthors
Shi J,Zheng L,Lin Z,Hou C,Liu W,Yan T,Zhu L,Wang Y,Lu L,Liu Zdoi
10.1016/j.jep.2015.04.019subject
Has Abstractpub_date
2015-07-01 00:00:00pages
183-94eissn
0378-8741issn
1872-7573pii
S0378-8741(15)00270-6journal_volume
169pub_type
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