[Study on the chiral separation of securinine by high-performance capillary electrophoresis and its stereoselective metabolism in rat].
OBJECTIVE
To 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.


METHODS
The 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-beta-CD as chiral selector. Determination was carried out with a UV detector at 254 nm. The separations were performed at 16 degrees C 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.


RESULTS
The experimental results showed that the concentration of HP-beta-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 i.p. administration, the rats excreted more d-securinine than l-securinine through bile, urine and feces. The metabolism process in rats was stereoselective.


CONCLUSIONS
This method is simple, reliable and suitable for studying the stereoselective metabolism of securinine in rats.
Li
Xiao-hai
XH
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Zhang
Jin-lan
JL
Zhou
Tong-hui
TH
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D001646:Bile / Q000378:metabolism; D019075:Electrophoresis, Capillary / Q000379:methods*; D019665:Euphorbiaceae / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D008297:Male; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D000470:Alkaloids; D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D010880:Piperidines; C000785:securinine