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目的建立丹参素在比格犬血浆中的高效液相色谱分析方法,并利用此方法研究丹参素经口服给药后在比格犬体内的药物代谢动力学行为。方法选用咖啡酸作为内标物质,用乙酸乙酯对血浆中药物进行萃取。采用Agilent 1200高效液相色谱系统,Zorbax SB-C18色谱柱(250 mm×4.6 mm,5μm),以0.1%甲酸-乙腈溶液系统为流动相进行梯度洗脱,流速1.0 mL/min,进样量100μL,检测波长280 nm。比格犬按丹参素9 mg/kg单剂量口服给予丹参素载药微丸后,测定不同时间血药浓度,并用WinNolin软件计算药动学参数。结果丹参素标准曲线线性范围为0.09～7.20μg/mL(r=0.9999),此范围内线性关系良好;提取回收率为74.3%～89.1%,最低定量浓度为0.04μg/mL。血药浓度平均达峰时间为1.08 h,平均峰浓度为3.06μg/mL。结论此方法简便、稳定、准确,可用于丹参素在比格犬体内药物代谢动力学研究。
OBJECTIVE To establish a HPLC method for the determination of Danshensu in Beagle dog plasma and to study the pharmacokinetics of Danshensu in Beagle dog after oral administration. Methods Caffeic acid was used as the internal standard substance, and the drugs in plasma were extracted with ethyl acetate. The mobile phase was eluted with a 0.1% formic acid-acetonitrile solution on a Zorbax SB-C18 column (250 mm × 4.6 mm, 5 μm) using an Agilent 1200 HPLC system with a flow rate of 1.0 mL / min. 100μL, detection wavelength 280 nm. Beagle dogs danshensu drug-loaded pellets by a single dose of 9 mg / kg Danshensu, the blood concentration was measured at different times, and pharmacokinetic parameters were calculated using WinNolin software. Results The linear range of Danshensu standard curve was 0.09 ~ 7.20μg / mL (r = 0.9999). The linear range was within the range of 74.3% ~ 89.1%. The lowest concentration was 0.04μg / mL. The average peak plasma concentration of 1.08 h, the average peak concentration of 3.06μg / mL. Conclusion This method is simple, stable and accurate and can be used to study the pharmacokinetics of Danshensu in Beagle dogs.