摘要
目的:建立LC-MS/MS测定大鼠血浆中的马钱子碱和士的宁含量,以溶剂萃取法提取大鼠血浆中的待测成分。方法:以他克林为内标,采用Agilent ZORBAX XDB-C18色谱柱,流动相为乙腈-甲醇-水(0.05%甲酸,10 nmol.L-1甲酸铵)梯度洗脱,质谱采用多反应监测(MRM),用于定量分析的离子对依次为m/z 395.2/324.2(马钱子碱),m/z 335.2/184.2(士的宁)和m/z 199.1/171.1(他克林)。结果:测定血浆样品2种成分的线性范围分别为0.195~100,0.078 1~40μg.L-1,相关系数分别为0.994,0.996,马钱子碱的提取回收率为78.9%~102.4%,士的宁的提取回收率为95.2%~106.1%,方法的精密度、准确度、基质效应和稳定性均符合要求。结论:方法专属性强、灵敏度高,适用于血浆马钱子类生物碱的药代动力学研究。囊泡制剂能够降低马钱子碱进入体循环的药物浓度,且具有缓释作用。
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. Method: Samples were extracted by ethyl acetate-nbutanol (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. 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. Result: The method was linear in the range of 0. 195-100 and 0. 078-40 ug . 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 Cmax were (26. 20 ±5.81 ) and ( 12. 50 ±3.00) ug . L-1 while the AUC0-∞ were ( 193.75 ±39.43) and (98.25 ±28.54) ug . h . L-1 of the two components. Conclusion: We conclude that the niosomes may reduce the systemic exposures and prolong the local release of brucine and strychnine.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2012年第6期853-857,共5页
China Journal of Chinese Materia Medica
基金
国家"重大新药创制"科技重大专项(2009ZX09103-395)
国家中医药管理局项目(06-07ZP49)