Ashraf Ahmed, ElDin Norhan Badr, Rostom Yasmin, El-Zeany Badr A, Sedik Ghada A
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
BMC Chem. 2024 Jul 19;18(1):133. doi: 10.1186/s13065-024-01238-8.
Ensuring the quality control of active pharmaceutical ingredients is crucial for drug products being introduced into the market. Even for established drugs, it is necessary to maintain a cutting-edge impurity control system. To analyze caffeine and chlorphenoxamine hydrochloride in their binary mixture, as well as theophylline and chlorphenoxamine N-oxide as related substances, a reversed phase-high performance liquid chromatography combined with a diode array detector system was created. The chromatographic separation was conducted using a C18 X-select Waters® column. The mobile phase consisted of 20.0 mM potassium dihydrogen phosphate modified to pH 3 with o-phosphoric acid and methanol. A gradient elution program was adopted at a flow rate of 1.3 mL/min and detected at a wavelength of 222 nm. The present methodology demonstrates a concentration ranging from 2-60, 1-80, 0.5-20 to 0.4-20 µg/mL for chlorphenoxamine hydrochloride, caffeine, chlorphenoxamine N-Oxide and theophylline, respectively. Chlorphenoxamine N-Oxide, being an impurity of chlorphenoxamine was prepared by refluxing intact drug with 5% HO for 24 h at 100 °C. One of the objectives of the analytical community is to promote the adoption of green analysis methods, which involve the development of environmentally friendly techniques. The levels of greenness and whiteness were evaluated using four specific tools: Eco-Scale System, GAPI, AGREE, and RGB tool. Furthermore, we have evaluated the greenness of the analytical method presented and compared its performance and greenness to that of the approach described in the literature. In this study, results from CPX and CAF analysis were compared to those obtained in a previous study. The result shows that there is no notable variation in precision and accuracy. The proposed method was validated in accordance with the requirements of ICH.
确保活性药物成分的质量控制对于即将推向市场的药品至关重要。即使对于已上市的药物，维持一个前沿的杂质控制系统也是必要的。为了分析二元混合物中的咖啡因和盐酸氯苯那敏，以及作为相关物质的茶碱和氯苯那敏N -氧化物，创建了一种反相高效液相色谱结合二极管阵列检测器系统。色谱分离使用C18 X - select Waters® 柱进行。流动相由用邻磷酸调节至pH 3的20.0 mM磷酸二氢钾和甲醇组成。采用梯度洗脱程序，流速为1.3 mL/min，检测波长为222 nm。本方法分别显示盐酸氯苯那敏、咖啡因、氯苯那敏N -氧化物和茶碱的浓度范围为2 - 60、1 - 80、0.5 - 20至0.4 - 20 μg/mL。氯苯那敏N -氧化物作为氯苯那敏的杂质，通过将完整药物与5%的过氧化氢在100°C下回流24小时制备。分析界的目标之一是推广采用绿色分析方法，这涉及开发环境友好型技术。使用四种特定工具评估绿色度和白度水平：生态尺度系统、GAPI、AGREE和RGB工具。此外，我们评估了所提出的分析方法的绿色度，并将其性能和绿色度与文献中描述的方法进行了比较。在本研究中，将CPX和CAF分析的结果与先前研究中获得的结果进行了比较。结果表明，精密度和准确度没有显著差异。所提出的方法根据ICH的要求进行了验证。
