An isocratic HPLC method has been developed and validated for estimating paracetamol and diclofenac sodium simultaneously with three skeletal muscle relaxants, namely, methocarbamol, tizanidine hydrochloride and chlorzoxazone in their pure standard mixtures and in different multi-component dosage forms in a single chromatographic run. HPLC separation was achieved on a C18 Inertsil ODS-3V 5 μm column (250 × 4.6 mm) using a mobile phase mixture containing acetonitrile and 25 mM phosphate buffer (pH 7.4 adjusted with NaOH) in the proportion of (39.7:60.3, v/v) pumped at 1.2 mL/min flow rate with UV detection at 220 nm. An experimental design was used by applying Plackett–Burman design for screening the most critical predictors affecting the chromatographic separation and Box–Behnken design for optimizing the selected predictors and creating the response surface between the selected predictors and the interested responses. ICH recommendations were applied for validating the proposed method with regard to linearity, precision, accuracy, selectivity, limits of detection and quantitation, and robustness. There are many applications for the optimized method that can be applied for routine estimation of the cited drugs in laboratories of quality control and pharmaceutical industries to save money and time and to reduce material waste and effort.

中文翻译：

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应用 Box-Behnken 设计和响应面方法选择同时测定三种不同药物剂型中扑热息痛和双氯芬酸钠以及三种骨骼肌松弛剂的最佳 RP-HPLC 条件

我们开发并验证了等度 HPLC 方法，可在单次色谱运行中同时测定纯标准混合物中的扑热息痛和双氯芬酸钠以及三种骨骼肌松弛剂（即美索巴莫、盐酸替扎尼定和氯唑沙宗）以及不同多组分剂型中的含量。使用含有乙腈和 25 mM 磷酸盐缓冲液（用 NaOH 调节 pH 7.4）的流动相混合物，在 C18 Inertsil ODS-3V 5 μm 柱（250 × 4.6 mm）上实现 HPLC 分离，比例为（39.7:60.3，v/ v) 以 1.2 mL/min 流速泵送，并在 220 nm 处进行 UV 检测。采用实验设计，应用 Plackett-Burman 设计筛选影响色谱分离的最关键预测变量，并应用 Box-Behnken 设计优化所选预测变量并在所选预测变量和感兴趣的响应之间创建响应面。ICH 建议用于验证所提出的方法的线性、精密度、准确度、选择性、检测和定量限以及稳健性。优化方法有许多应用，可用于质量控制和制药行业实验室中所引用药物的常规评估，以节省金钱和时间，并减少材料浪费和工作量。