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目的:建立并验证同时测定大鼠组织中去甲基麻黄碱、去甲基伪麻黄碱、麻黄碱、伪麻黄碱、甲基麻黄碱、苦杏仁苷和野樱苷的UPLC-MS/MS,分析大鼠口服麻黄-杏仁药对水提物后有效成分在主要脏器组织中的分布情况。方法:参照FDA生物样本分析方法的方法学验证指南完成该测定的方法验证。采用盐酸苯海拉明和葛根素2种内标物分别对5种麻黄生物碱和苦杏仁苷、野樱苷进行定量分析。结果:该方法灵敏可靠,9种化合物(含3对差向异构体)在18 min内快速分离。麻黄生物碱在各组织中广泛分布;苦杏仁苷在体内分布较少,组织中(脑除外)可检测到其代谢产物野樱苷。与体外药物原形不同,D-野樱苷在组织中峰浓度(心、肝、脾、肺、肾中质量分数分别为170.5,112.8,98.4,152.3,381.7 ng·g~(~(-1)))低于L-野樱苷(心、肝、脾、肺、肾依次为906.4,652.3,177.4,500.9,2 060.4 ng·g~(~(-1)))。结论:建立的LC-MS/MS适用于大鼠口服麻黄-杏仁药对水提物后的组织分布研究。D-野樱苷在组织分布减少可能是麻黄-杏仁药对毒性拮抗作用的内在体现。麻黄生物碱和苦杏仁苷、野樱苷在肺组织中均有较高分布,这可能与两药协同平喘的药效学机制有关。
OBJECTIVE: To establish and validate UPLC-MS / MS for the simultaneous determination of demethylephedrine, demethylated pseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, amygdalin and wild cherry glycosides in rats. Ephedrine - almonds on the water extract of the active ingredient in the distribution of the major organs and tissues. Methods: Refer to FDA Methodology for Validation of Biological Samples for validation guidelines for method validation of this assay. Two kinds of internal standard of diphenhydramine hydrochloride and puerarin were used to quantitatively analyze five kinds of ephedrine alkaloids, amygdalin and wild cherry glycosides. Results: The method was sensitive and reliable. Nine compounds (including three epimers) were rapidly separated in 18 min. Ephedra widely distributed in various tissues; amygdalin in the body less distributed in the tissue (except the brain) can be detected in its metabolites wild cherry glycosides. Different from the in vitro pharmacokinetics, the peak concentrations of D-wild cherry glycosides in the tissues (170.5, 112.8, 98.4, 152.3, and 381.7 ng · g ~ (-1) )) Was lower than that of L-wild cherry glycosides (heart, liver, spleen, lung, kidney, followed by 906.4,652.3,177.4,500.9,2 060.4 ng · g ~ (-1))). Conclusion: The established LC-MS / MS is suitable for oral administration of ephedra - almonds on the tissue distribution of water extract. D-wild cherry glycosides in the organization may reduce the distribution of ephedra - almonds on the toxicity of the inherent embodiment. Ephedrine alkaloids and amygdalin, wild cherry glycosides were higher in the lung tissue distribution, which may be synergistic with the two drugs asthma pharmacodynamic mechanism.