Simultaneous determination of four alkaloids in mice plasma and brain by LC-MS/MS for pharmacokinetic studies after administration of Corydalis Rhizoma and Yuanhu Zhitong extracts.

A sensitive and selective liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of tetrahydropalmatine, coptisine, palmatine and dehydrocorydaline in mice plasma and brain after intraperitoneal administration of the extracts of Yuanhu Zhitong (YZ) and Corydalis Rhizoma (CR). Biological samples were processed with ethyl acetate extraction. The mobile phase consisted of acetonitrile and water (containing 10mM ammonium acetate, adjusted with acetic acid to pH 4.25) with gradient elution at a flow rate of 0.4mL/min. Detection was performed on a triple quadrupole mass spectrometer using positive ion ESI in the multiple reaction monitoring (MRM) mode. The calibration curves for all analytes had good linearity (r(2)>0.9910). The intra- and inter-day precisions (RSD) were within 13.9%, and accuracy (RE) was between -12.0% and 13.7%. This method was successfully applied to the pharmacokinetic and brain distribution study after administration of the extracts of YZ and CR. The pharmacokinetic study indicated that the AUC of plasma and brain increased, and the CL of the two matrixes decreased after administration of YZ when compared with CR (p<0.05). The four analytes could cross the blood-brain barrier in vivo and elucidate the potentials for the treatment of diseases of the central nervous system.