构建中国肾移植患者他克莫司治疗药物监测网络平台,方便医生管理患者信息,并且为患者提供群体、亚群体和个体3个不同层次的治疗药物监测。通过使用数据库管理系统MySQL软件建立和管理医生信息数据库以及患者信息数据库,使用超文本标记语言(hypertext mark-up language,HTML)和Java语言的JSP(Java server pages)技术研制患者信息数据库的网络管理平台,为医生提供数据库管理功能;在已建立好的群体药物动力学模型的基础上,运用以上编程语言研制群体和亚群体预测功能模块;根据贝叶斯原理和最大后验概率密度函数,建立目标函数,选择最优化算法,研制个体预测功能模块。网络平台能够为医生提供管理患者数据库功能和3个水平的预测功能,为肾移植患者服用他克莫司个体化给药提供指导,并为其他药物的治疗药物监测网络平台的研制提供模板。
An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard （IS） was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deproteinated with 10% （v/v） perchloric acid. Separation was achieved on a UltimateTM AQ-C18 column （250 mm×4.6 mm, 5 μm） with a mobile phase （pH 5.05） composed of acetonitrile-water （31：69, v/v, containing 0.002 M sodium dodecyl sulfate, 0.0125 M potassium dihydrogen phosphate, 0.015 M triethylamine） at a flow rate of 1.0 mL/min. The calibration curve was linear （r〉0.994） between 7.5 and 4000 ng/mL. The lower limit of quantification （LLOQ） was 7.5 ng/mL. The precision was validated and the relative standard deviation was in the range of 1.87% to 15.70%; the accuracy was between 93.98%-106.89%. The mean recoveries were 95.40% and 95.31% for metformin and IS, respectively. The relative error （RE） of stability at different storage conditions was within ±9.00%. This method was used to determine the concentration-time profile of metformin in diabetic rat plasma following an oral administration of metformin at the dose of 10 mg/kg. Our results indicated that ion-pair HPLC-UV method using UltimateTM AQ-C18 column was effective for the pharmacokinetic studies of high polarity compounds like metformin.
