黄芪注射液在正常和甲亢模型大鼠体内药动学比较

Comparative Pharmacokinetics Study of Astragalus Injection in Normal and Hyperthyroid Model Rats

关键词:  黄芪注射液  高效液相色谱-串联质谱法  甲亢模型大鼠  药动学

Key words:  Astragalus injection  LC-MS/MS  hyperthyroid model rats  pharmacokinetics

摘要:

目的 建立大鼠血浆中黄芪甲苷浓度的高效液相色谱-串联质谱（LC-MS/MS）测定方法，并比较黄芪注射液在正常和甲亢模型大鼠体内的药动学。方法 采用蛋白质沉淀法处理血浆样品，色谱柱为Ultimate^TM XB-C₁₈柱（4.6 mm×50 mm，5 μm），流动相采用水-乙腈梯度洗脱，柱温为30℃；流速为0.6 mL·min^–1。质谱采用电喷雾离子源正离子模式，选择离子反应监测模式。结果 黄芪甲苷在5~1 000 ng·mL^–1内线性良好，该方法准确度和精密度、提取回收率和基质效应、稳定性均符合生物基质样品测试要求。与正常大鼠的药动学参数比较，甲亢模型大鼠体内黄芪甲苷的AUC和MRT显著降低，CL_z和V_z显著增加（P<0.05）。表明黄芪甲苷在甲亢模型大鼠体内较正常大鼠的AUC降低，代谢显著加快。结论 建立的大鼠血浆中黄芪甲苷浓度测定的LC-MS/MS方法简便灵敏，准确可行，适用于黄芪注射液在大鼠体内的药动学研究。

Abstract:

OBJECTIVE To establish a high performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for determining astragaloside IV in rat plasma and to compare pharmacokinetics of Astragalus injection in normal and hyperthyroid model rats. METHODS The plasma sample was handled by protein precipitation. The column was Ultimate^TM XB-C₁₈ column(4.6 mm×50 mm, 5 μm) with the mobile phase of water and acetonitrile by gradient elution at 0.6 mL·min^-1. The column temperature was 30℃. The electrospray ion source with positive ion mode and select the ion reaction monitoring mode were used. RESULTS The linear range of Astragaloside IV was 5-1 000 ng·mL^-1. The precision, accuracy, mean recoveries, matrix effects and stability were satisfied with the requirements of biological sample measurement. Compared with the pharmacokinetic parameters of normal group, the AUC and MRT of astragaloside IV decreased significantly with the CL_z and V_z increased significantly in hyperthyroid model rats. Compared with normal rats, the AUC decreased and the rate of metabolism was significant acceleration in hyperthyroid model rats. CONCLUSION The established LC-MS/MS method for the determination of astragaloside IV in rat plasma is simple, sensitive, accurate and feasible, which is suitable for the pharmacokinetic study of Astragalus injection in rats.