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目的:建立HPLC-荧光法测定犬血浆中紫花前胡苷的浓度,初步研究紫花前胡苷在犬体内的药代动力学特征。方法:以乙腈为蛋白沉淀剂,以Hypersil BDS C18柱(200 mm#4.6 mm,5μm)为色谱柱,流动相为甲醇-0.1%磷酸溶液(45∶55);激发波长为360 nm;发射波长为395 nm。Beagle犬4只,单次静脉注射紫花前胡苷30 mg·kg-1,后肢静脉取血,采用HPLC测定血药浓度,并用DAS 2.0程序计算药代学参数。结果:Beagle犬血浆中内源性成分对测定无干扰,紫花前胡苷的线性范围为0.1～40.0μg·mL-1(r=0.9993),平均相对回收率为89.8%～100.7%,日内和日间RSD均<10%。紫花前胡苷在犬体内的药代动力学过程符合开放二房室模型,主要药代动力学参数t1/2α、t1/2β、V1、CL和AUC(0-t)分别为(0.536±0.085)h、(3.048±0.826)h、(0.446±0.038)L·kg-1、(0.417±0.108)L·h-1.kg-1和(68.966±16.181)mg·L-1.h。结论:本方法准确、灵敏、快速,适用于紫花前胡苷的血药浓度测定和药代动力学研究,为紫花前胡苷的开发和临床应用提供参考。
OBJECTIVE: To establish a HPLC-fluorescence method for the determination of purpurin in canine plasma and to study the pharmacokinetics of purpurin in dogs in vivo. Methods: The mobile phase consisted of methanol-0.1% phosphoric acid solution (45:55) with Hypersil BDS C18 column (200 mm # 4.6 mm, 5 μm) as mobile phase with acetonitrile as the precipitant. The excitation wavelength was 360 nm. 395 nm. Four Beagle dogs were injected intravenously with 30 mg · kg -1 of promethazine, blood was drawn from the hindlimb venous, plasma concentration was determined by HPLC, and pharmacokinetic parameters were calculated by DAS 2.0 program. Results: The endogenous components of Beagle dog’s plasma did not interfere with the determination. The linear range of purpurin was 0.1-40.0μg · mL-1 (r = 0.9993), the average relative recovery was 89.8% -100.7% Daytime RSD was <10%. The pharmacokinetics of purpurin in dogs was in accordance with the open two-compartment model. The main pharmacokinetic parameters t1 / 2α, t1 / 2β, V1, CL and AUC (0-t) were (0.536 ± 0.085) h, (3.048 ± 0.826) h, (0.446 ± 0.038) L · kg -1, (0.417 ± 0.108) L · h -1 · kg -1 and (68.966 ± 16.181) mg · L -1 · h, respectively. Conclusion: The method is accurate, sensitive and rapid. It is suitable for the determination of prodrugs and the pharmacokinetics of prodrugs. It provides a reference for the development and clinical application of prussianosin.