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

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AtlanticsT3(100mm×3.0mm,3μm),流动相为乙腈-水(10∶90),对18名健康受试者单剂量口服150mg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3.00ng·mL-1,每个生物样品分析时间仅为2min。18名健康受试者口服天麻素胶囊150mg后,测定血浆样品并估算天麻素的药动学参数,Tmax均值为(0.8±0.3)h,t1/2均值为(2.1±0.4)h,Cmax均值为(378±84)ng·mL-1,AUC0-12均值为(878±175)ng·h·mL-1,AUC0-∞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。

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 Tmax were （0.8±0.3）h, the t1/2 were （2.15±0.38）h, the Cmax were （378±84） ng·mL^-1, the AUC0-12 were （878±175） ng·h·mL^-1,the AUC0-∞ 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.