STUDY ON THE CHIRAL SEPARATION OF SECURININE BY HIGH-PERFORMANCE CAPILLARY ELECTROPHORESIS AND ITS STEREOSELECTIVE METABOLISM IN RAT

AIMTo establish a high-performance capillary electrophoresis (HPCE) chiral separation method for D-securinine and l-securinine, and use this method to investigate the stereoselective metabolism process of D- and l-securinine in Wistar rats. METHODSThe electrophoretic condition and parameters were investigated and the optimized conditions were as following: the electrophoretic medium was 40 mmol·L^-1 Tris-H₃PO₄ buffer (pH adjusted to 6.0 with H₃PO₄) containing 32 mmol·L^-1 HP-β-CD as chiral selector. Determination was carried out with a UV detector at 254 nm. The separations were performed at 16℃ with a positive voltage of 15 kV. Samples were injected into the capillary by pressure for 6 s. The biological samples (urine, bile, plasma and feces) of rats were alkalized and extracted with ethyl acetate. RESULTSThe experimental results showed that the concentration of HP-β-CD, the concentration of the running buffer and the pH value of the buffer were the main important factors which effected the resolution. D-Securinine and l-securinine were separated at baseline level under the determination conditions. The determination was not interfered by endogenous components and metabolites. After ip administration, the rats excreted more D-securinine than l-securinine through bile, urine and feces. The metabolism process in rats was stereoselective. CONCLUSIONThis method is simple, reliable and suitable for studying the stereoselective metabolism of securinine in rats.