[关键词]
[摘要]
目的 建立大鼠血浆中红景天苷及其苷元酪醇的测定方法,并研究其药物动力学。方法 取大鼠10只灌胃给予红景天苷100 mg·kg-1,检测给药前和给药后24 h内红景天苷及酪醇的血浆浓度,并计算其药动学参数。采用液相色谱-串联质谱法,以水杨苷为内标,色谱柱为Alltima C18,流动相:甲醇-水(80 ∶ 20),等度洗脱,流速为0.3 mL·min-1,柱温为40 ℃,电喷雾负离子源,红景天苷、酪醇和水杨苷的选择检测离子质荷比(m/z)分别为299.2→119.6,137.1→119.0和285.1→122.9。结果 红景天苷和酪醇检测浓度的线性范围分别为50~5000(r=0.9991)、5~500(r=0.9994) ng·mL-1,最低检测限分别为6.25,2.5 ng·mL-1;药动学参数:红景天苷的t1/2β为(5.67±0.84) h,Cmax为(3914.7±915.8),AUC0→24 h为(8434.2±213.8) ng·h·mL-1;酪醇的t1/2β为(6.24±0.91) h,Cmax为(289.3±44.6) ng·mL-1,AUC0→24 h为(1236.7±73.4) ng·h·mL-1。结论 本方法专属性强、灵敏度高、准确性好,可用于红景天苷和酪醇的血药浓度测定,红景天苷和酪醇在大鼠体内的药动学符合二室模型特征。
[Key word]
[Abstract]
Objective To establish a method to determine the plasma concentration of salidroside and its aglycone metabolite tyrosol in rat by using LC-MS/MS,and to calculate the pharmacokinetic parameters of salidroside and its aglycone metabolite tyrosol in rat after oral administration of 100 mg·kg-1 salidroside. Methods Ten rats were given intragastric gavage of 100 mg·kg-1 salidroside,the plasma concentrations of salidroside and tyrosol were detected before administration and within 24 hours after administration,and then the pharmacokinetics parameters were examined. LC-MS/MS was performed on Alltima C18(100×2.0 mm,5 μm)column with salicin as the internal standard. Mobile phase consisted of 80 % methanol-water solution,and flow rate was 0.3 mL·min-1. The temperature of column was 40 ℃. The LC-MS/MS system was operated by using an electrospray ionization probe in the negative ion mode. Scan mode was in multiple reaction ion monitoring(MRM) mode. The ion of monitor was m/z 299.2→119.6 for salidroside,m/z 137.1→119.0 for tyrosol,and m/z 285.1→122.9 for salicin(internal standard)respectively. Results The linear ranges of salidroside and tyrosol were 50 ~ 5000 ng·mL-1(r = 0.9991)and 5~500 ng·mL-1(r = 0.9994) respectively. The lowest limit of quantification(LLOQ) of salidroside and tyrosol were 6.25 ng·mL-1 and 2.5 ng·mL-1. The pharmacokinetic parameters of t1/2β,Cmax,and AUC0→24 h were as follows:(5.67±0.84)h,(3914.7±915.8)ng·mL-1,and (8434.2±213.8)ng·h·mL-1 for salidroside, and(6.24±0.91)h,(289.3±44.6)ng·mL-1,and(1236.7±73.4)ng·h·mL-1 for tyrosol. Conclusion A sensitive,accuracy and suitable LC-MS/MS method for determining salidroside and tyrosol has been developed and successfully applied to the pharmacokinetic study of salidroside after oral administration in rats.
[中图分类号]
R285.5
[基金项目]