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基于理想性函数的多目标优化策略在血浆和制剂中罗格列酮和格列美脲的电泳分离和定量中的应用。

Multi-objective optimization strategy based on desirability functions used for electrophoratic separation and quantification of rosiglitazone and glimepiride in plasma and formulations.

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.

出版信息

Drug Test Anal. 2012 Jan;4(1):39-47. doi: 10.1002/dta.260. Epub 2011 Mar 18.

Abstract

Multiple response simultaneous optimization employing Derringer's desirability function was used for the development of a capillary electrophoresis method for the simultaneous determination of rosiglitazone (RSG) and glimepiride (GLM) in plasma and formulations. Twenty experiments, taking the two resolutions, the analysis time, and the capillary current as the responses with three important factors--buffer morality, volte and column temperature--were used to design mathematical models. The experimental responses were fitted into a second order polynomial and the six responses were simultaneously optimized to predict the optimum conditions for the effective separation of the studied compounds. The separation was carried out by using capillary zone electrophoresis (CZE) with a silica capillary column and diode array detector at 210 nm. The optimum assay conditions were 52 mmol l⁻¹ phosphate buffer, pH 7, and voltage of 22 kV at 29 °C. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The assay limit of detection was 0.02 µg ml⁻¹ and the effective working range at relative standard deviation (RSD) of ≤ 5% was 0.05-16 µg ml⁻¹ (r = 0.999) for both drugs. Analytical recoveries of the studied drugs from spiked plasma were 97.2-101.9 ± 0.31-3.0%. The precision of the assay was satisfactory; RSD was 1.07 and 1.14 for intra- and inter-assay precision, respectively. The proposed method has a great value in routine analysis of RSG and GLM for its therapeutic monitoring and pharmacokinetic studies.

摘要

采用 Derringer 的适宜性函数对多响应进行同步优化,用于开发一种同时测定血浆和制剂中罗格列酮(RSG)和格列美脲(GLM)的毛细管电泳方法。采用 20 次实验,以两种分辨率、分析时间和毛细管电流作为响应,以三个重要因素——缓冲液的 pH 值、电压和柱温——作为响应,设计数学模型。实验响应拟合为二次多项式,同时优化六个响应,以预测有效分离研究化合物的最佳条件。采用硅烷毛细管柱和二极管阵列检测器在 210nm 处进行毛细管区带电泳(CZE)分离。最佳测定条件为 52mmol/L 磷酸盐缓冲液,pH7,29°C 时电压为 22kV。该方法在整个研究参数空间内显示出实验数据与预测值之间的良好一致性。检测限为 0.02μg/ml,在相对标准偏差(RSD)≤5%的有效工作范围内,两种药物的浓度范围为 0.05-16μg/ml(r=0.999)。从加标血浆中提取的研究药物的回收率为 97.2-101.9%±0.31-3.0%。该方法的精密度令人满意;日内和日间精密度的 RSD 分别为 1.07%和 1.14%。该方法对于 RSG 和 GLM 的治疗监测和药代动力学研究具有重要的常规分析价值。

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