Studies On Pharmacokinetics And Interactions Of Scutellaria-coptis Herb Couple

Herb couples as the basic composition units of Chinese herbal formulas have special clinical significance in traditional Chinese medicine (TCM), and are much simpler than other complex formulas without altering their basic therapeutic features. The combination of Radix Scutellariae and Rhizoma Coptidis, so called scutellaria-coptis herb couple, is the main herb couple in many TCMs, with characteristics of bitter and cold and common medicinal functions in purging fire for removing toxin, eliminating the wetness evil from the upper warmer, clearing away the heat-evil and expelling superficial evils.1. Development and validation of a LC-MS-MS method for simultaneous determination of the main components in scutellaria-coptis herb couple in rat plasma.A sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in scutellaria-coptis herb couple in rat plasma. After protein precipitation with acetonitrile and 0.1% NaH2PO4, chromatography was performed using a C18 column, with gradient elution with 0.1% formic acid and acetonitrile at 0.25 ml/min. All analytes including internal standards were monitored under positive ionization conditions by selected reaction monitoring with an electrospray ionization source. The lower limit of quantification was 10 ng/ml for baicalin, baicalein and wogonin, and 0.6 ng/ml for berberine, palmatine and jatrorrhizine. And intra-and inter-day assays were met the requirements.2. Application in pharmacokinetic studies of traditional Chinese medicinal preparations containing scutellaria-coptis herb couple in ratsThe method developed in this paper is used for the application in pharmacokinetic studies after oral administration of Yiqing Capsule and Gegen-Qinlian Tablet to rats. It is specific, high sensitivity, consistent with biological sample analysis requirements and can be used for the pharmacokinetic studies of traditional Chinese medicinal preparations containing scutellaria-coptis herb couple.3. Comparative pharmacokinetics of the main components in scutellaria-coptis after single, co-administration of scutellaria-coptisTo investigate the interactions in scutellaria-coptis herb couple, comparative pharmacokinetics of the main components in scutellaria-coptis after single, co-administration of scutellaria-coptis are studied in this part. Results showed co-administration of scutellaria-coptis herb couple, the bioavailabilities of the components in this herb couple were decreasing than single administration. Then the comparative pharmacokinetics of single and co-administration of baicalin and berberine were studied and showed the phenomenon may occur by the interactions of the main components in scutellaria-coptis herb couple.4. Metabolism of scutellaria-coptis herb couple in vitroIn order to evaluate the effect of the main components in scutellaria-coptis herb couple on P450 enzymes and elucidate the interactions on this herb couple, the metabolites of the specific substrate of P450 enzymes (CYP3A4, CYP2D6, CYP1A2 CYP2C9, CYP2C19 and CYP2E1) were determined using LC-MS-MS. Data showed both inhibited and excited effects were existed in scutellaria-coptis, and connecting with pharmacokinetic results, a further research on judging the substrate of CYP3A4 showed metabolism was not the reason for the interations on this herb couple.