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目的:建立丹参酮ⅡA血药浓度测定方法,并用于丹参酮ⅡA在Beagle犬体内的药动学研究。方法:采用高效液相色谱(HPLC)法。色谱柱为Phenomenex Luna C18,流动相为水(5 mmol/L醋酸铵+0.05%H3PO4)-乙腈,流速为1.0 ml/min,检测波长为270 nm,柱温为40℃,进样量为20μl。9只Beagle犬随机分为丹参酮ⅡA低、中、高剂量(2、4、8 mg/kg)组,分别于iv给药前及给药后2、5、10、15、20、30、45、60、75、90、120 min,从前肢静脉取血测定血药浓度,采用DAS 2.0软件计算药动学参数。结果:丹参酮ⅡA检测质量浓度线性范围为0.097 5~12.50μg/ml(r=0.999 8),精密度、稳定性试验的RSD均小于10%,方法回收率为100.4%~107.2%,提取回收率为90.2%~92.3%。丹参酮ⅡA低、中、高剂量组t1/2α分别为(1.01±0.27)、(1.03±0.46)、(1.51±0.65)min,t1/2β分别为(16.25±4.78)、(22.42±9.32)、(24.45±12.02)min,AUC0-120 min分别为(150.88±45.25)、(305.44±92.55)、(643.67±178.27)μg·min/ml,CL分别为(12.01±4.36)、(12.78±5.06)、(12.17±5.41)ml/(min·kg)。结论:本方法精密度、稳定性和准确度均符合生物样品测定要求,丹参酮ⅡA在Beagle犬体内AUC0-120 min与剂量呈现良好的线性关系。
Objective: To establish a method for the determination of tanshinone Ⅱ A in blood and to study the pharmacokinetics of tanshinone Ⅱ A in Beagle dogs. Methods: High performance liquid chromatography (HPLC) method was used. The chromatographic column was Phenomenex Luna C18 with a mobile phase of water (5 mmol / L ammonium acetate + 0.05% H3PO4) -acetonitrile at a flow rate of 1.0 ml / min with a detection wavelength of 270 nm and a column temperature of 40 ° C with a sample volume of 20 μl . Nine Beagle dogs were randomly divided into tanshinone ⅡA low, medium and high doses (2,4,8 mg / kg) group, respectively, before iv administration and after administration 2,5,10,15,20,30,45 , 60,75,90,120 min. Blood samples were taken from forelimb vein to determine plasma concentration. Pharmacokinetic parameters were calculated using DAS 2.0 software. Results: The linear range of tanshinone Ⅱ A was 0.097 5 ~ 12.50 μg / ml (r = 0.999 8). The RSDs of the precision and stability tests were all less than 10%. The recoveries were 100.4% ~ 107.2% 90.2% ~ 92.3%. The t1 / 2α of tanshinone ⅡA group was (1.01 ± 0.27), (1.03 ± 0.46) and (1.51 ± 0.65) min respectively, and the t1 / 2β were (16.25 ± 4.78) and (22.42 ± 9.32) (24.45 ± 12.02) min and (150.88 ± 45.25), (305.44 ± 92.55) and (643.67 ± 178.27) μg · min / ml respectively in AUC0-120 min and (12.01 ± 4.36) and (12.78 ± 5.06) , (12.17 ± 5.41) ml / (min · kg). Conclusion: The precision, stability and accuracy of this method are in line with the requirements of biological samples. Tanshinone Ⅱ A has a good linear relationship with the dose of AUC0-120 min in Beagle dogs.