[Determination of brucine and strychnine in rat after cutaneous administration of semen strychni niosome gel by LC-MS/MS].
OBJECTIVE
A sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the determination of brucine and strychnine in rat plasma.


METHODS
Samples were extracted by ethyl acetate-n-butanol (7: 3). Chromatographic separation was operated on ZORBAX XDB-C18 column with gradient elution of acetonitrile-methanol-water (0.05% acetic acid and 10 nmol x L(-1) ammonium formate contained), followed by LC-MS/MS in positive electrospray ionization. Quantification was carried out on multiple reaction monitoring (MRM) of the transition m/z 395.2/324.2, m/z 335.2/184.2 and m/z 199.1/171.1 for brucine, strychnine and tacrine (internal standard), respectively.


RESULTS
The method was linear in the range of 0.195-100 and 0.07840 microg x L(-1) for brucine and strychnine, with coefficient correlation 0.994 and 0.996 respectively. The recoveries of extraction were 78.9% - 102.4% for brucine and 95.2% - 106.1% for strychnine. Precision, accuracy, stability and matrix effect of the analytes met the requirement. The method was applied to a pharmacokinetic study of brucine and strychnine after cutaneous administration of Semen Strychni niosome gel. The C(max) were (26.20 +/- 5.81) and (12.50 +/- 3.00) microg x L(-1) while the AUC(0-infinity), were (193.75 +/- 39.43) and (98.25 +/- 28.54) microg x h x L(-1) of the two components.


CONCLUSIONS
We conclude that the niosomes may reduce the systemic exposures and prolong the local release of brucine and strychnine.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Jingya
J
Li
Fengru
F
Miao
Li
L
Lin
Dan
D
Zhu
Chengren
C
Lin
Jianxun
J
Liu
D000279:Administration, Cutaneous; D000700:Analgesics / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid; D003292:Convulsants / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D005782:Gels / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008297:Male; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry; D013047:Specific Pathogen-Free Organisms; D013331:Strychnine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics*; D031461:Strychnos nux-vomica / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
D000700:Analgesics; D003292:Convulsants; D005782:Gels; D008081:Liposomes; C083806:brucine; D013331:Strychnine