A validated RP-HPLC method was developed for the estimation of paracetamol, caffeine, metoclopramide and ergotamine simultaneously in bulk and pharmaceutical formulation. The method was extended for the determination of two paracetamol genotoxic and nephrotoxic impurities and degradation products namely p-aminophenol and 4-chloroacetanilide. Separation was done on octadecyl column (15 cm × 2.1 mm, 5 μm). Gradient elution was performed using mobile phase consisting of acetonitrile and water (pH 3) in ratio of (20: 80, v/v) for the first 3 min, (50: 50, v/v) for the next 4.5 min, then (20: 80, v/v) for the final 2.5 min. The flow rate was 0.7 mL/min throughout the run which took 10 min. UV detection was done at 230 nm. The proposed method agreed with ICH guidelines of method validation. The suggested method was applied for the estimation of the proposed drugs in their dosage form. Statistical comparison was done between the results obtained from the suggested method and those obtained from reported HPLC method. The proposed method is more beneficial than the published one because of having higher sensitivity and selectivity as it allows the detection of the proposed drugs in lower concentrations in the presence of paracetamol toxic impurities, p-aminophenol and 4-chloroacetanilide.

中文翻译：

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对氨基苯酚和 4-氯乙酰苯胺存在下抗偏头痛四元混合物的定量测定

开发了一种经过验证的 RP-HPLC 方法，用于同时估计散装和药物制剂中的扑热息痛、咖啡因、甲氧氯普胺和麦角胺。该方法扩展到测定两种对乙酰氨基酚遗传毒性和肾毒性杂质和降解产物，即对氨基苯酚和 4-氯乙酰苯胺。在十八烷基柱 (15 cm × 2.1 mm, 5 μm) 上进行分离。使用由乙腈和水 (pH 3) 组成的流动相进行梯度洗脱，前 3 分钟为 (20:80, v/v)，接下来 4.5 分钟为 (50:50, v/v)，然后(20: 80, v/v) 最后 2.5 分钟。在整个运行过程中流速为 0.7 mL/min，耗时 10 分钟。在 230 nm 处进行 UV 检测。建议的方法与 ICH 方法验证指南一致。所建议的方法被用于估计所建议药物的剂型。对从建议方法获得的结果与从报告的 HPLC 方法获得的结果进行了统计比较。所提出的方法比已发表的方法更有益，因为它具有更高的灵敏度和选择性，因为它允许在对乙酰氨基酚有毒杂质、对氨基苯酚和 4-氯乙酰苯胺的存在下检测较低浓度的拟议药物。