毛细管柱内聚醚砜膜的制备及其对生物样品中4种降糖药的初步分离

Preparation of Polyethersulfone Membrane in Capillary Column and the Preliminary Separation of Hypoglycemic Agents in Biological Samples

采用原位相转换法在毛细管进样端制备聚醚砜膜(PESM),以盐酸二甲双胍峰面积和牛血清白蛋白(BSA)拦截率为评价指标,经单因素考察和正交试验优化PESM的制备方法。获得的最优条件为:以18%聚醚砜和6%聚乙二醇600为成膜液,成膜液温度为45℃,挥发时间为60s,并依此条件制备3批PESM进行验证。采用PESM在柱偶联高效毛细管电泳方法(PESM-HPCE)分离BSA或大鼠血浆中的盐酸二甲双胍、格列美脲、盐酸罗格列酮和瑞格列奈,结果表明PESM将大分子物质(BSA和血浆内源性成分)拦截在膜外,4种小分子降糖药则全部被检出,分离度和药物峰面积的精密度良好,但PESM的流体阻力作用使药物峰后移。本试验所得的PSEM在8h内稳定。用制备的3批PESM以直接进样方式分析BSA溶液中的4种降糖药,药物峰面积和迁移时间的批间RSD(n=3)值分别小于4.09%和3.14%。另外,采用PESM-HPCE法直接进样分析BSA溶液或兔血浆中的异烟肼、维生素B1和B12,结果PESM均可有效拦截生物大分子,检出药物。

Polyethersulfone membrane (PESM) was prepared with in situ phase conversion method in capillary injection inlet. Single factor and orthogonal experiments were used to optimize the preparation conditions of PESM with the determined peak area of metformin hydrochloride and interception rate of macromolecular bovine serum albumin (BSA) as indicators. The optimum membrane-forming scheme was 18% of polyethersulfone, 6% of polyethylene glycol (PEG) 600, the membrane temperature of 45 ℃ and the volatilization time of 60 s. The PESM in column coupled high performance capillary electrophoresis (PESM-HPCE) method was established for the simultaneous analysis of metformin hydrochloride, glimepiride, rosiglitazone hydrochloride and repaglinide in the BSA solution or rat plasma sample. The four hypoglycemic agents in the biological samples were directly determined by a dialysis injection method. The results showed that the PESM had good interception effects on BSA and plasma endogenous components. The four hypoglycemic agents were well detected and the precisions of the peak area were good. However, the retention time of four drugs was increased due to the fluid resistance of PESM. The PESM was stable within 8 h. Three batches of PESM were prepared and the sample of four hypoglycemic agents in BSA was analyzed. The batch-to-batch RSDs of peak area and migration time for four hypoglycemic drugs were less than 4.09% and 3.14%, respectively. Moreover, isoniazid, vitamins B1 and B12 in BSA or rabbit plasma were all detected by this PESM-HPCE method, indicating biomacromolecular components could be intercepted by PESM.