HPLC法测定小鼠血浆中洋川芎内酯Ⅰ的浓度及药动学研究  

HPLC determination of senkyunolideⅠ in mice plasma and its pharmacokinetics

作　　者：熊耀坤[1,2] 林晓[1] 梁爽[1] 于泽[1] 杜焰[1] 冯怡[1] 

机构地区：[1]上海中医药大学中药现代制剂技术教育部工程研究中心,上海201203 [2]江西中医学院,南昌330004

出　　处：《药物分析杂志》2013年第3期371-375,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：国家教育部科学技术研究重点项目(211060);上海市科委上海市自然科学基金项目(11ZR1434500);上海市教委科研创新项目(11zz112);上海市教委重点学科(J50302);上海市教委科研创新项目(重点)(12ZZ124)

摘　　要：目的:建立测定小鼠血浆中洋川芎内酯Ⅰ浓度的高效液相色谱方法,并应用于药动学研究。方法:小鼠单剂量静注或灌胃给予(104 mg·kg-1)洋川芎内酯Ⅰ,在给药后不同时间取血,血浆经沉降蛋白处理后,采用HPLC法测定洋川芎内酯Ⅰ的浓度,使用Megres-C18色谱柱(150 mm×4.6 mm,5μm),以乙腈-2.0%冰醋酸(1∶3,v/v)为流动相,流速为1.0 mL·min-1,柱温为30℃,洋川芎内酯H为内标,检测波长278 nm。结果:在0.075～30 mg·L-1范围内,洋川芎内酯Ⅰ在血浆中线性关系良好,定量下限为0.075 mg·L-1,方法回收率大于85%,日内日间RSD均小于5%,样品在室温下放置24 h,-4℃放置5 d,经过3次冻融循环后基本稳定。小鼠静注给药后主要药代动力学参数分别为t1/231.93 min,AUC(0-∞)2738.80 mg·min·L-1,MRT(0-∞)31.61 min;小鼠灌胃给药后主要药代动力学参数分别为t1/240.07 min,AUC(0-∞)892.42 mg·min·L-1,MRT(0-∞)61.38 min。经计算,洋川芎内酯Ⅰ在小鼠体内的绝对生物利用度为32.19%。结论:所建立的方法可靠,简便快速,适用于洋川芎内酯Ⅰ小鼠体内血药浓度测定及药代动力学的研究。Objective：To establish an HPLC method for the determination concentration of senkyunolide I in mice plasma for pharmacokinetic study. Methods： The mice were intravenously administrated of a single dose or intragas- tricly administrated senkyunolide I（ 104 mg · kg-1）. The plasma samples after protein settlement processing were analyzed for the senkyunolide I concentration by HPLC. The Megres - C18 （150 mm× 4. 6 mm,5 μm）column was adopted,the mobile phase was acetonitrile-0.2% glacial acetic acid（ 1：3 ,v/v）at a flow rate of 1.0 mL · min-1 under 30 ℃, the senkyunolide H was marked as the internal standard, and the detection wavelength was set at 278 nm. Results： Excellent liner relationship was obtained in the range of 0.075 to 30 mg · L - 1, the limit determination of senkyunolide I was 0.075 mg · L -1. The recovery of the method was more than 85% ,and the intra - and inter - day RSDs were less than 5 %. The samples were stable for 24 h at room temperature ,5 days at -4 ℃, and remained stable after three freeze -thaw cycles. The pharmacokinetic parameters were as follows： t1/2 31.93 rain, AUC（0-∞） 2738.80 mg. min. L-1,MRT（0-∞） 31. 61 rain in mice with intravenous administration, and t1/2 40. 07 min, AUC （0-∞ ） 892.42 mg · min · L-1, MRT（0-∞ ） 61.38 min in mice with intragastric administration. The absolute bio- availability of senkyunolide I in mice was calculated to be 32.19%. Conclusion： The method is reliable, simple, rapid, and suitable for the pharmacokinetic study and determination of senkyunolide I in plasma.

关 键 词：高效液相色谱法 川芎 洋川芎内酯Ⅰ 小鼠 药代动力学 绝对生物利用度 

分 类 号：R917[医药卫生—药物分析学]