吸波面积-高效液相色谱法联用研究养血注射液在Beagle犬体内的药动学

Pharmacokinetics of Yangxue Injection in Beagle Dogs by the Method of Area Under the AbsorbanceWavelength Curve Combined with High Performance Liquid Chromatography

目的研究组分制剂养血注射液在Beagle犬体内的动态过程,探讨复杂成分体系药动学评价的可行性。方法通过静脉滴注,不同时间点采集的血浆样品,处理后经紫外-可见分光光度法在200~350 nm下全波长扫描,计算吸光度-波长曲线下面积(简称吸波面积),得到给药后不同时间Beagle犬体内养血注射液中阿魏酸钠、盐酸川芎嗪、丹参素钠的混合血药浓度;同时,采用高效液相色谱法分别测定不同时间血浆中阿魏酸钠、盐酸川芎嗪、丹参素钠各单一成分的血药浓度。通过3P97程序分别对2种方法获得的血药浓度-时间数据进行拟合,获得药动学参数。结果吸波面积法结果显示,养血注射液混合药物在Beagle犬体内的药时过程符合二室模型,c0为84.94μg·mL-1,t1/2(β)为46.94 min,AUC为3 227.77μg·min·mL-1。HPLC结果表明,阿魏酸钠、盐酸川芎嗪的药时过程呈单室模型,c0、t1/2和AUC分别为37.02、0.54μg·mL-1,26.24、32.35 min和1 406.75、20.50μg·min·mL-1;丹参素钠呈二室模型,c0为48.48μg·mL-1,t1/2β为59.21 min,AUC为1 842.06μg·min·mL-1。吸波面积法获得的养血注射液混合血药浓度比HPLC获得的各单一成分血药浓度大,混合AUC与阿魏酸钠、盐酸川芎嗪、丹参素钠三者药物的AUC之和接近,生物半衰期均较短。结论吸波面积法和高效液相色谱法联合使用能较好地阐述养血注射液在Beagle犬体内的药动学特征,为西药复方、组分中药以及复杂体系的中药复方制剂药动学研究和评价提供了科学思路和可行途径。

OBJECTIVE To discuss the availability of evaluation on pharmacokineties for the system of complicated components by studying the in vivo blood dynamic change of Beagle dogs from Yangxue injection in interval time. METHODS Yangxue injection were administered to dogs by intravenous infusion, plasma samples were collected at different times and treated with methanol to precipitate protein. Area under the absorbanee-wavelength curve （AUAWC） and total concentration of sodium ferulate, tetramethylpyrazine hydrochlo- ride and tanshinol sodium in plasma were obtained after a full ultraviolet-visible spectrum scan to samples from 200 to 350 nm wavelength. Meanwhile, individual concentrations of sodium ferulate, tetramethylpyrazine hydrochloride and tanshinol sodium in plasma were deter- mined by HPLC method. The pharmacokinetic parameters by the method of AUAWC and HPLC were obtained after processed with 3P97 procedure from Chinese Pharmacology Institute. RESULTS To Yangxue injection with multieomponent, the former appeared to have a two-compartment model in the Beagle dogs, with pharmacokineties＇ parameters co 84. 94 μg·mL^- l, elimination half-life （ tl/2β ） 46. 94 min and area under concentration versus time （AUC） 3 227.77 min·μg·mL^-1. The results of the latter by HPLC demonstrated that so- dium ferulate and tetramethylpyrazine hydrochloride appeared to have a one-compartment model in the Beagle dogs, co were 37. 02 and 0. 54 p^g ~ mL^-l ,t1/2 were 26. 24 and 32. 35 min,AUC were 1 406. 75 and 20. 50 μg · min · mL^-1. Tanshinol sodium appeared to have a two-compartment model in the Beagle dogs, with pharmacokineties＇ parameters co 48.48 μg·mL^-l, elimination half-life （tl/2β） 59. 21 min and AUC 1 842. 06 μg·min · mL^-1. The results indicated that the total components concentration in plasma and AUC got through the way of AUAWC were greater than that of a single component by HPLC. CONCLUSION The pharmaeokinetic characteristics of Yangxue injection in Beagle dogs is shown by the method of AUAWC, which will bring a feasible idea and pathway to pharmacokinetics＇ studies of chemicals compound, traditional Chinese medicine with multicomponents and complicated compound of traditional Chinese med- icine under the combination between the method of AUAWC and HPLC.