Study on the pharmacokinetic profiles of corynoline and its potential interaction in traditional Chinese medicine formula Shuanghua Baihe tablets in rats by LC-MS/MS

摘要

Corynoline, the major isoquinoline alkaloid component derived from Colydalis bungeana Herba, has greatly impressed many scientists due to its various pharmacological effects. However, there is little information on its pharmacokinetics. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry method has been developed and validated for the determination of corynoline in rat plasma. The calibration curve showed good linearity within the concentration range of 0.01-20 ng/mL. The method was fully validated and successfully applied in a pharmacokinetic study of corynoline in rats, in which the rats were treated with corynoline, corynoline combined with berberine and the traditional Chinese medicine formula Shuanghua Baihe tablets (SBT, containing corynoline, berberine and other ingredients), respectively. Corynoline showed low bioavailability and a high elimination rate. The terminal elimination half-life was prolonged about 3-fold, and the maximum plasma concentration (C.), area under the plasma concentration-time curve (AUC(0-12)) of corynoline were increased by 46.5% and 34.2%, respectively, when the same dosage of corynoline was administered in SBT. Furthermore, compared with the corynoline group, the C. and AUC(0-12) were increased by 11.1-fold and 5.0-fold respectively, in the rats treated with corynoline combined with berberine. The results suggested that oral administration of the SBT prolonged the elimination half-life of corynoline and increased its bioavailability. Berberine played an important role in the pharmacokinetic drug-drug interaction of corynoline and ingredients in SBT, and the influence of other co-existing compounds in SBT on the pharmacokinetic profiles of corynoline could not be ignored. (C) 2015 Elsevier B.V. All rights reserved.