Abstract

Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A “dual-mode” gradient high-performance liquid chromatography method was developed, where the separation was achieved via “dual-mode” gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 μm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.

中文翻译：

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使用双模式梯度HPLC和TLC密度测定法同时测定扑热息痛杂质中的扑热息痛，扑热息痛和咖啡因

摘要

验证了两种色谱方法在两种PC的存在下测定对乙酰氨基酚（PC）（最近已整合到COVID-19的支持治疗中），丙氮平（PZ）和咖啡因（CF）的广泛处方的止痛和解热药物组合杂质，即4-氨基苯酚和4-硝基苯酚。开发了“双模式”梯度高效液相色谱方法，该方法通过改变三元流动相的组成（乙腈：甲醇：水）和流速通过“双模式”梯度实现分离。这样可以在相对较短的分析时间内获得良好的分辨率。使用Zorbax Eclipse XDB色谱柱C18（5μm（250×4.6 mm））和UV检测器设置为220 nm进行分析。另一种方法是薄层色谱光密度法，其中使用由氯仿：甲苯：乙酸乙酯：甲醇：乙酸（6：6：1：1：2：0.1，按体积计）组成的流动相进行分离。在硅胶60 F254板上于220nm进行光密度检测。所开发的方法已按照ICH指南进行了充分验证，并被证明是准确，可靠，特异的，适合用作纯度指示方法，用于纯形式的PC或质量控制实验室中带有PZ和CF的药物的常规分析。