HPLC-MS/MS法研究PVP包衣去甲斑蝥素壳聚糖纳米粒在大鼠体内的药代动力学

Study on pharmacokinetic profile of PVP-coated norcantharidin-chitosan nanoparticles in rats by HPLC-MS/MS

目的:建立HPLC-MS/MS方法测定大鼠血浆中去甲斑蝥素(NCTD)浓度,并考察PVP包衣去甲斑蝥素-壳聚糖纳米粒制剂(PVP coated NCTD-chitosan nanoparticles,PVP-NCTD-NP)在大鼠体内药代动力学及相对生物利用度。方法:使用电喷雾电离负离子源(ESI-),多重反应离子(MRM)模式检测药物;采用高氯酸作为蛋白沉淀剂,测定大鼠尾静脉注射PVP-NCTD-NP和原药NCTD溶液后的血药浓度;利用3P97软件计算药代动力学参数。结果:NCTD在0.102 5～10.25μg·mL-1范围内线性关系良好(r=0.999 2),最低检测限为50 ng·mL-1;经3P97软件拟合,NCTD的药代动力学过程符合二室模型,与原药相比,PVP-NCTD-NP相对生物利用度为325.5%。结论:本法灵敏、准确、选择性高,适用于NCTD药代动力学的研究;PVP-N-CTD-NP可促进药物的吸收,显著提高NCTD的生物利用度。

Objective：To establish an HPLC-MS/MS method for the determination of norcantharidin（NCTD）,and to study the bioavailability and pharmaceutical characteristics of PVP-coated NCTD-Chitosan nanoparticles（PVP-NCTD-NP） in SD rats.Methods：Negative electrospray ionization（ESI-） with selected multi reaction monitoring（MRM） mode was used.Perchloric acid was adopted as protein precipitation agent.NCTD concentrations in rat plasma were determined after intravenous injection of PVP-NCTD-NP and NCTD solution.Pharmacokinetic parameters were calculated by 3P97 program.Results：The linear range was 0.1025～10.25μg·mL-1（r=0.9992）,and the detection limit was 50ng·mL-1.The concentration-time data was fitted to a two-compartment model,while the relative bioavailability of PVP-NCTD-NP to NCTD was 325.5%.Conclusion：The method is sensitive,accurate,highly selective,and applicable to the pharmacokinetic study of NCTD.PVP-NCTD-NP formulation can promote the absorption of NCTD,and its bioavailability is significantly improved.