类风湿关节炎患者雷公藤甲素血清浓度测定及其药动学研究

目的建立雷公藤甲素血药浓度的超高效液相色谱检测法,并对类风湿关节炎患者口服雷公藤多苷片后雷公藤甲素的体内药代动力学进行初步探讨。方法入组3例类风湿关节炎患者,其血清以艾司唑仑为内标,用乙酸乙酯进行提取后进样测定。色谱柱为Waters Acquity C18柱(2.1 mm×100 mm,1.7μm),流动相为乙腈-0.1%冰乙酸(30∶70),流速为0.2 mL/min,柱温为30℃,检测波长为220 nm。血药浓度数据用DAS2.1.1药动学计算机程序处理。结果雷公藤甲素与内标物分离良好,保留时间分别为4.9、8.9 min左右。雷公藤甲素血药浓度在13.13~840.00 ng/mL范围内,峰面积与内标物峰面积比值之间的线性关系良好,日内、日间精密度均RSD15%,回收率为88.25%~99.33%。雷公藤甲素药动学参数Cmax、Tmax、T1/2β、AUC0-12 h分别为(159.97±42.43)ng/mL、(1.33±0.58)h、(7.51±2.26)h、(1131.12±89.20)mg?h/L。结论雷公藤甲素药动学符合二室模型,吸收迅速,个体之间存在差异。

Determination of Serum Concentration of Triptolide in Patients with Rheumatoid Arthritis and Its Pharmacokinetics Study

Objective To establish an UPLC method for determination of Triptolide in serum and explore its pharmacokinetics in patients with rheumatoid arthritis after oral administration of tripterygium glycosides tablet. Methods Three patients with rheumatoid arthritis were enrolled. Using Estazolam as internal standard, serum was extracted with acetic ether, and determination was performed on column of Waters Acquity C18 （2.1 mm×100 mm, 1.7 μm） with mobile phase consisted of acetonitrile-0.1% glacial acetic acid （30∶70） at the flow rate of 0.2 mL/min. The column temperature was 30 ℃, and the detection wavelength was set at 220 nm. The serum concentration of Triptolide was processed by DAS 2.1.1 computer program. Results Triptolide was well-separated from internal standard, and the retention time were about 4.9 min and 8.9 min, respectively. Linear range of Triptolide was 13.13-840.00 ng/mL. RSD of intra-day and inter-day were lower than 15%and the recoveries were 88.25%-99.33%. Pharmacokinetic parameters were as follows：Cmax was （159.97±42.43） ng/mL, Tmax was （1.33±0.58） h, T1/2βwas （7.51±2.26） h, and AUC0-12 h was （1131.12±89.20） mg？h/L, respectively. Conclusion Pharmacokinetics of Triptolide conformed to two compartment model. Triptolide can be quickly absorbed, and exists differences among individuals.