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

BACKGROUND

The Bile-processed (BRC), which has a colder drug property than (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 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 of berberine and palmatine increased two times and the T of the three alkaloids decreased three times after bile processing. AUC and AUC 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 (RC) were determined by UPLC-MS/MS.The whole pharmacokinetic profiles of three alkaloids in the bile-processed (BRC) were similar to those of RC.The shorter T and increased 2-fold C were obtained after RC bile-processing.Bile-processing could promote the absorption rate of alkaloids in a certain degree. RC: , BRC: Bile-processed , 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: maxium of drug concentration, T: time for maxium of drug concentration, AUC: area under concentration-time curve, LLOQ: Linearity and lower limits of quantification, t: half-life, Clz: body clearance.