Comparative Pharmacokinetic Profiles of Three Protoberberine-type Alkaloids from Raw and Bile-processed Rhizoma coptidis in Heat Syndrome Rats

BACKGROUND: The Bile-processed Rhizoma coptidis (BRC), which has a colder drug property than Rhizoma coptidis (RC), is widely used for the treatment of heat syndrome. We compared the pharmacokinetics of the protoberberine-type alkaloids in BRC and RC in rats with heat syndrome to elucidate the bile-processing mechanism. MATERIAL AND METHODS: We established a rapid and sensitive method for simultaneously determining three alkaloids: berberine, palmatine, and jatrorrhizine, in rat plasma based on ultra-performance liquid chromatography/tandem mass spectrometry. The separation was carried out on a Waters ACQUITY BEA C(18) column. The mobile phase consisted of acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid and 10 mmol/L ammonium acetate) and carbamazepine was used as an internal standard. The detection was carried out in a multiple reaction monitoring mode (MRM) using electrospray ionization in the positive ion mode. RESULTS: Pharmacokinetic profiles indicated that the C(max) of berberine and palmatine increased two times and the T(max) of the three alkaloids decreased three times after bile processing. AUC(0→∞) and AUC(0→t) of the alkaloids were similar between RC and BRC. CONCLUSION: The results suggest that bile processing could increase the absorption rate of alkaloids. This study broadens our understanding of Chinese herbal medicine processing. SUMMARY: Contents of berberine, palmatine and jatrorrhizine, in heat syndrome rats’ plasma between the raw and bile-processed Rhizoma coptidis (RC) were determined by UPLC-MS/MS. The whole pharmacokinetic profiles of three alkaloids in the bile-processed Rhizoma coptidis (BRC) were similar to those of RC. The shorter T(max) and increased 2-fold C(max) were obtained after RC bile-processing. Bile-processing could promote the absorption rate of alkaloids in a certain degree. Abbreviation Used: RC: Rhizoma coptidis, BRC: Bile-processed Rhizoma coptidis, HPLC: high-performance liquid chromatography, UPLC-MS/MS: ultra-performance liquid chromatography-mass spectrometry/ mass spectrometry, LC-MS: liquid chromatography-mass spectrometry, MRM: multiple reaction monitoring mode, QC: quality control, RE: relative error, RSD: relative standard deviation, C(max): maxium of drug concentration, T(max): time for maxium of drug concentration, AUC: area under concentration-time curve, LLOQ: Linearity and lower limits of quantification, t(1/2): half-life, Clz: body clearance