功劳木提取物中三种生物碱类成分在大鼠体内的药动学研究  

Pharmacokinetics of three Alkaloids from Mahonia bealei extract in rats

作　　者：曹慧坤 王瀚扬 刘有平[1] 王鑫[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]本溪市高级中学,辽宁本溪117000

出　　处：《沈阳药科大学学报》2017年第12期1060-1066,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立用于同时测定大鼠血浆中药根碱、木兰花碱和巴马汀的LC-MS/MS分析方法,并将该方法用于功劳木提取物在大鼠体内的药动学研究。方法大鼠灌胃给予功劳木提取物后,眼眶静脉丛取血,蛋白沉淀法处理血浆样品,色谱柱为Agilent ZORBAX SB-C18(50 mm×4.6 mm,5μm),流动相采用乙腈-5 mmol·L^(-1)乙酸铵(含体积分数0.2%甲酸),体积比为35∶65等度洗脱,以正离子扫描选择反应监测(SRM)模式进行检测。结果药根碱、木兰花碱和巴马汀质量浓度分别在5.0~320.0、2.0~648.0和2.5~200.0μg·L^(-1)内线性关系良好,日内和日间精密度均小于15.0%,准确度均在±3.9%以内,提取回收率均在70.0%以上。药根碱的主要药动学参数t_(max)、t_(1/2)、ρ_(max)、AUC0-t分别为(0.50±0.16)h、(7.34±4.91)h、(141.11±74.72)μg·L^(-1)、(208.27±95.25)μg·h·L^(-1);木兰花碱的t_(max)、t_(1/2)、ρ_(max)、AUC0-t分别为(0.11±0.04)h、(4.79±4.26)h、(366.60±135.65)μg·L^(-1)、(305.54±176.29)μg·h·L^(-1);巴马汀的t_(max)、t_(1/2)、ρ_(max)、AUC0-t分别为(0.25±0.08)h、(5.16±3.58)h、(56.60±33.75)μg·L^(-1)、(112.60±56.61)μg·h·L^(-1)。结论该方法快速、选择性好,适用于大鼠灌胃给予功劳木提取物后药根碱、木兰花碱和巴马汀在大鼠体内的药动学研究。药根碱、木兰花碱和巴马汀在大鼠体内吸收均较迅速。Objective To establish an LC-MS/MS method for simultaneous determination of jatrorrhizine, magnoflorine and palmatine in rat plasma and apply to in vivo pharmacokinetic study of Mahonia bealei extract in rats. Methods After i. g. administration of Mahonia bealei extract to rats, plasma samples were collected via the the post-orbital venous plexus and treated by protein precipitation. The analytical column was Agilent ZORBAX SB-C18 （50 mm × 4. 6 mm,5 μm）and the mobile phase was acetonitrile-5 mmol-L- 1 ammonium acetate（ 0. 2% formic acid） （ V： V = 35 ： 65 ） with isocratic elution. Detection was performed by selective reaction monitoring （SRM） mode via positive electrospray ionization. Results The method was linear over the concentration ranges of 5.0 - 320. 0 μg · L - 1 for jatrorrhizine, 2. 0 - 648.0 μg ·L - 1 for magnoflorine and 2. 5 -200. 0 μg. L- 1 for palmatine. The intra-day and inter-day precisions were less than 15.0% ,the relative errors were all within s4. 0%, and the extraction recoveries were above 70. 0%. The pharmacokinetic parameters of jatrorrhizine including tmax ,tl/2 ,Pmax ,AUC0., were as follows： （0. 50 ±0. 16）h, （7.34 ± 4. 91 ） h, （ 141.11 ± 74. 72 ） I-~g＂ L - 1, （ 208.27± 95.25 ） μg·h. L - 1 ; The tmax, t1/2 ,/9max and AUC0.t of magnoflorine were （0. 11 s 0. 04 ） h, （4. 79 s 4.26 ） h, （ 366. 60 ± 135.65 ） μg · L-1 and （ 305.54 ±176. 29） μg.h·L-1 ,respectively. The tmax ,t1/2 ,Pmax and AUC0-1 of palmatine were（0. 25 ±0. 08）h, （5.16 ± 3.58）h, （56. 60 ±33.75） μg.L-1 and（ 112. 60 ± 56. 61 ） μg.h.L-1 ,respectively. Conclusions The method is fast and selective, and suitable to study the pharmacokinetics of jatrorrhizine, magnoflorine and palmatine in rats after i. g. administration of Mahonia bealei extract.

关 键 词：功劳木 药根碱 木兰花碱 巴马汀 药代动力学 

分 类 号：R917[医药卫生—药物分析学]