天麻素血药浓度测定及药动学研究

Determination of Gastrodin in Human Plasma by LC-MS/MS and Its Application in Pharmacokinetic Study

关键词:  天麻素  LC-MS/MS  药动学

Key words:  gastrodin  LC-MS/MS  pharmacokinetic

摘要:

目的 建立天麻素血浆药物浓度LC-MS/MS测定法，测定健康受试者血浆中天麻素的浓度并评价天麻素胶囊的药动学。方法 建立以阿昔洛韦为内标的天麻素血药浓度LC-MS/MS测定方法，色谱柱为Atlantics T3(100 mm×3.0 mm，3 μm)，流动相为乙腈-水(10∶90)，对18名健康受试者单剂量口服150 mg天麻素胶囊进行药动学研究。结果 建立了简单、专属的天麻素血浆药物浓度的LC-MS/MS测定法，以沉淀法进行样品前处理，无杂质干扰测定，灵敏度达到了3.00 ng∙mL^-1，每个生物样品分析时间仅为2 min。18名健康受试者口服天麻素胶囊150 mg后，测定血浆样品并估算天麻素的药动学参数，T_max均值为(0.8±0.3)h，t_1/2均值为(2.1±0.4)h，C_max均值为(378±84)ng∙mL^-1，AUC_0-12 均值为(878±175)ng∙h∙mL^-1，AUC_0-∞均值为(897±175)ng∙h∙mL^-1。结论 本法快速、准确、灵敏度高且前处理简单，能很好的应用于药动学研究。

Abstract:

OBJECTIVE To determine the plasma concentration of gastrodin and evaluate the pharmacokinetics of the gastrodin capsule. METHODS We developed an LC-MS/MS assay method using aciclovir as the internal standard to determine the plasma concentration of gastrodin. An Atlantics T3 column (100 mm×3.0 mm, 3 μm) and the mobile phase of CH3CN-water (10∶90) were used for LC-ESI (-) and MRM for MS. RESULTS A simple and specific method has been developed to determinate the plasma concentrations of gastrodin by LC-MS/MS. Each plasma sample was preprocessed by adding methanol, and analysised within 2 minutes. No significant interfering peaks were observed. The lower limit of quantitation was 3.00 ng∙mL^-1. An oral dose of gastrodin capsules was given to 18 healthy male volunteers. The pharmacokinetic parameters of the test capsule were as follows: the T_max were (0.8±0.3)h, the t_1/2 were (2.15±0.38)h, the C_max were (378±84) ng∙mL^-1, the AUC_0-12 were (878±175) ng∙h∙mL^-1，the AUC_0-∞ were(897±175)ng∙h∙mL^-1, respectively. CONCLUSION The method is simple in pretreatment and is rapid, sensitive and accurate in analysis. This method was successfully applied to study the pharmacokinetics of gastrodin in healthy Chinese volunteers.