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目的:建立测定兔体内丹参酮ⅡA的HPLC方法,并考察丹参酮ⅡA聚乳酸载药纳米粒(TS-PLA-NP)兔体内药代动力学特征。方法:家兔耳缘静脉注射TS-PLA-NP和丹参酮ⅡA溶液,在设定时间点从颈静脉取血制样,以吉非罗齐为内标,采用HPLC-MS法测定丹参酮ⅡA在兔体内的血药浓度及药物组织分布,药动学参数采用DAS2.0进行统计。结果:吉非罗齐和丹参酮ⅡA在该条件下的保留时间分别为10.5、14.5 min。TS-PLA-NP在家兔体内的t1/2由丹参酮ⅡA的2.573 h延长到4.117 h;MRT0～∞由2.585 h延长到6.033 h,峰浓度由0.21 mg/L减少到0.134 mg/L。静脉给药后2 h,丹参酮ⅡA纳米药物组肝脏和肿瘤中的浓度均高于丹参酮ⅡA组;丹参酮ⅡA以纳米的剂型给药后2 h,肝脏中的药物浓度提高了5倍以上,肿瘤中的药物浓度提高了近9倍;心、肾、脾、肺等组织中药物浓度均明显降低;血液中浓度下降了近10倍。结论:丹参酮ⅡA聚乳酸载药纳米粒在兔体内具有良好的缓释和肝靶向特征。
OBJECTIVE: To establish a HPLC method for the determination of tanshinone Ⅱ A in rabbits and to study the pharmacokinetics of tanshinone ⅡA polylactic acid-loaded nanoparticles (TS-PLA-NP) in rabbits. Methods: TS-PLA-NP and tanshinone Ⅱ A solution were injected intravenously into the ear vein of rabbits. Gemfibrozil was taken as internal standard at the set time point. The content of tanshinone ⅡA In vivo plasma concentration and drug distribution, pharmacokinetic parameters using DAS2.0 statistics. Results: The retention time of gemfibrozil and tanshinone ⅡA under these conditions were 10.5 and 14.5 min, respectively. The t1 / 2 of TS-PLA-NP in tibolone was prolonged from 2.573 h to 4.117 h in tanshinone ⅡA. The peak of MRT0 ~ ∞ was prolonged from 2.585 h to 6.033 h, and the peak concentration decreased from 0.21 mg / L to 0.134 mg / L. The concentration of tanshinone ⅡA nano-drug group in liver and tumor was higher than that of tanshinone ⅡA group 2 h after intravenous administration. The drug concentration in liver increased more than 5-fold 2 h after tanshinone ⅡA dosage form, Of the drug concentration increased nearly 9 times; heart, kidney, spleen, lung and other tissues were significantly lower drug concentrations; blood concentration decreased nearly 10 times. Conclusion: Tanshinone ⅡA polylactic acid-loaded nanoparticles have good sustained-release and liver-targeting characteristics in rabbits.