Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (...Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) specify six impurities, viz.;impurities A, B, C, D, E and F, respectively for its active pharmaceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature;however, there is no report related to impurity E. The prospects to the formation and controlling of impurity E up to -0.03% in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.展开更多
目的：建立反相高效液相色谱法（RP-HPLC）测定卡维地洛片有关物质。方法：采用YMC-Pack Pro C8色谱柱（150 mm×4.6 mm,5μm）,以乙腈-0.02 mol·L-1磷酸二氢钾溶液（用磷酸调p H 2.0）为流动相进行梯度洗脱,流速1.0 m L·...目的：建立反相高效液相色谱法（RP-HPLC）测定卡维地洛片有关物质。方法：采用YMC-Pack Pro C8色谱柱（150 mm×4.6 mm,5μm）,以乙腈-0.02 mol·L-1磷酸二氢钾溶液（用磷酸调p H 2.0）为流动相进行梯度洗脱,流速1.0 m L·min-1,柱温30℃,检测波长为220 nm（杂质E）和240 nm（其他杂质）。结果：卡维地洛与已知杂质及强制破坏实验产生的降解产物均能获得良好的分离,杂质D（4-环氧丙烷氧基咔唑）与杂质E[2-（2-甲氧基苯氧基）乙胺]质量浓度分别在0.063 98～12.80μg·m L-1（r=0.999 9）和0.089 33～8.933μg·m L-1（r=1.000）范围内与峰面积呈良好的线性关系。杂质D高、中、低浓度的回收率（n=3）分别为98.6%、96.5%、94.2%,RSD分别为1.1%、0.8%、1.4%;杂质E高、中、低浓度的回收率（n=3）分别为99.2%、86%、92.7%,RSD分别为0.15%、0.65%、9.5%。杂质D和杂质E精密度试验的RSD（n=6）分别为1.4%和0.31%,建立的方法与现行中国药典收载的方法相比能分离检测到更多的杂质。结论：本方法经方法学验证,可用于卡维地洛有关物质的检测和质量控制。展开更多
Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound ...Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qualitative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ketoconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation products, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.展开更多
文摘Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) specify six impurities, viz.;impurities A, B, C, D, E and F, respectively for its active pharmaceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature;however, there is no report related to impurity E. The prospects to the formation and controlling of impurity E up to -0.03% in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.
文摘Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qualitative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ketoconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation products, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.
