附子6种生物碱在比格犬体内药动学研究  

Pharmacokinetic Study of Six Aconitine Alkaloids in Aconiti Lateralis Radix Praeparata in Beagle Dogs

作　　者：肖日平[1] 赖小平[1,2] 赵亚[1] 喻良文[1] 朱跃兰[3] 李耿[1] 

机构地区：[1]广州中医药大学中药学院,广东广州510006 [2]东莞广州中医药大学中医药数理工程研究院,广东东莞523808 [3]北京中医药大学东方医院,北京100078

出　　处：《中药材》2014年第2期284-287,共4页Journal of Chinese Medicinal Materials

基　　金：国家重点基础研究发展计划(973计划)课题(2009CB522803)

摘　　要：目的:研究口服附子后乌头碱、新乌头碱、次乌头碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、苯甲酰新乌头原碱在比格犬体内的药动学特征。方法:口服给予比格犬附子煎煮液后,采用固相萃取法处理血浆样品,应用UPLC-MS/MS方法对乌头类生物碱进行定量,采用ESI正离子模式,多反应监测方式检测,色谱柱为WATERS ACQUITY UPLC BEH C18(100 mm×2.1 mm,1.7μm),以甲醇-0.2%甲酸水溶液为流动相,以0.25 mL/min的流速进行梯度洗脱;内标法定量,检测乌头碱、新乌头碱、次乌头碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、苯甲酰新乌头原碱在各时间点内的血药浓度。采用DAS 2.1药代动力学程序计算主要药动学参数。结果:乌头碱、新乌头碱、次乌头碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、苯甲酰新乌头原碱的药动学曲线经拟合均符合口服给药的一室模型。结论:本实验同时对附子所含6种生物碱进行药动学研究,可以很好应用与监测口服附子后有效浓度的变化情况,从而达到增效减毒的作用,为附子的临床治疗及安全应用提供参考依据。Objective ：To study the phammcokinetics characteristics of six Aconitum alkaloids aconitine（ AC）, mesaconitine（ MA）, hypaconitine（ HA）, benzoylaconine （ BAC）, benzoylmesaconine （BMA） and benzoylhypaconine （BHA） in beagle dogs. Methods ： An ul- tra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） method was developed for simultaneous quantitation of six Aconitum alkaloids in beagle dog plasma after oral administration of Aconiti Lateralis Radix Praeparata decoction. UPLC/MS/MS system coupled with an electrospray ionization （ESI） source was performed in multiple-reaction monitoring（MRM） mode. Sample prepa- ration was performed with solid-phase extraction（SPE） on a 3 mL HLB cartridge before the analysis. The separation was applied on a Waters qa column（100 mm ×2. 1 mm,l. 7 μm） and a gradient elution of methanol and 0. 2% fomlic acid-water was used as mobile phase. The pharmacokinetic parameters were calculated by the results of the analysis through the DAS 2. 1 software（ Drug and Statistics for Windows）. Results ：The results showed that the fitting model for the six kconitum alkaloids was the one-compartment model pharma- cokinetics. Conclusion：The method is successfully used for the phat=lacokinetic evaluation of the six Aconitum alkaloids in beagle dog plasma, it can help nmnitor the ADME/Tox process when taking Aconiti Lateralis Radix Praeparata by observing the pharmacokinetic process. The results provide a good reference for clinical treatment and safe application of Aconiti Lateralis Radix Praeparata.

关 键 词：附子 超高效液相色谱-质谱联用法 乌头类生物碱 药代动力学 

分 类 号：R285.5[医药卫生—中药学]