Skibinski Robert, Trawinski Jakub
Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, Lublin 20-090, Poland.
J Chromatogr Sci. 2017 Mar 1;55(3):309-315. doi: 10.1093/chromsci/bmw186.
The untargeted chemometric methodology for the impurity profiling of amisulpride pharmaceutical formulations was successfully applied and developed. For this purpose a fast, accurate and specific analytical method was elaborated with the use of ultra high pressure liquid chromatography coupled with high resolution hybrid electrospray ionization quadrupole time of flight mass spectrometer in a fast polarity switching mode. All the obtained chromatographic profiles were aligned and a multivariate chemometric analysis including principal component analysis and partial least square (PLS) was performed. The developed PLS-DA pattern recognition model allowed the identification of all the analyzed pharmaceutical formulations of amisulpride as well as their manufacturers. Additionally, six impurities of amisulpride were identified by the use of MS/MS fragmentation and one of them was found as the main impurity (Imp-1) and can be regarded as the primary impurity "marker" for the analyzed formulations. Furthermore, one new impurity of amisulpride was found and its chemical structure was proposed (4-amino-5-(ethylsulfinyl)-2-methoxy-N-[(1-ethylpyrrolidin-2-yl)methyl]benzamide).
一种用于氨磺必利药物制剂杂质剖析的非靶向化学计量学方法得以成功应用和开发。为此，利用超高压液相色谱与高分辨率混合电喷雾电离四极杆飞行时间质谱仪在快速极性切换模式下，精心设计了一种快速、准确且特异的分析方法。对所有获得的色谱图进行对齐，并进行了包括主成分分析和偏最小二乘法（PLS）在内的多元化学计量学分析。所开发的PLS-DA模式识别模型能够识别所有分析的氨磺必利药物制剂及其制造商。此外，通过MS/MS裂解鉴定出六种氨磺必利杂质，其中一种被发现是主要杂质（Imp-1），可被视为所分析制剂的主要杂质“标志物”。此外，还发现了一种氨磺必利新杂质，并提出了其化学结构（4-氨基-5-（乙基亚磺酰基）-2-甲氧基-N-[(1-乙基吡咯烷-2-基)甲基]苯甲酰胺）。
