PDF(Pubmed)
Abstract：
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% H2O2 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.
摘要：
确保活性药物成分的质量控制对于将药物产品引入市场至关重要。即使是既定的药物，有必要保持先进的杂质控制系统。为了分析二元混合物中的咖啡因和盐酸氯苯那敏，以及茶碱和氯苯那敏N-氧化物作为相关物质，建立了反相高效液相色谱与二极管阵列检测器系统。使用C18X-选择的Waters®柱进行色谱分离。流动相由用正磷酸和甲醇改性至pH3的20.0mM磷酸二氢钾组成。以1.3mL/min的流速采用梯度洗脱程序,并在222nm的波长下检测。本方法表明，盐酸氯苯那敏的浓度范围为2-60、1-80、0.5-20至0.4-20µg/mL，咖啡因,氯苯那敏N-氧化物和茶碱，分别。氯苯那敏N-氧化物,通过将完整的药物与5%H2O2在100°C下回流24小时来制备氯苯那明的杂质。分析界的目标之一是推动采用绿色分析方法,其中涉及环保技术的发展。使用四个特定工具评估绿色和白度的水平：生态尺度系统，GAPI,同意,和RGB工具。此外，我们已经评估了所提出的分析方法的绿色性，并将其性能和绿色性与文献中描述的方法进行了比较。在这项研究中,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，精度和准确度没有明显变化。根据ICH的要求对所提出的方法进行了验证。
