Das Partha Pratim, Guzzinati Giulio, Coll Catalina, Gomez Perez Alejandro, Nicolopoulos Stavros, Estrade Sonia, Peiro Francesca, Verbeeck Johan, Zompra Aikaterini A, Galanis Athanassios S
NanoMegas SPRL, Boulevard Edmond Machtens 79, B1080 Brussels, Belgium.
Electron Crystallography Solutions SL, Calle Orense 8, 28020 Madrid, Spain.
Polymers (Basel). 2020 Jun 27;12(7):1434. doi: 10.3390/polym12071434.
Organic and biological compounds (especially those related to the pharmaceutical industry) have always been of great interest for researchers due to their importance for the development of new drugs to diagnose, cure, treat or prevent disease. As many new API (active pharmaceutical ingredients) and their polymorphs are in nanocrystalline or in amorphous form blended with amorphous polymeric matrix (known as amorphous solid dispersion-ASD), their structural identification and characterization at nm scale with conventional X-Ray/Raman/IR techniques becomes difficult. During any API synthesis/production or in the formulated drug product, impurities must be identified and characterized. Electron energy loss spectroscopy (EELS) at high energy resolution by transmission electron microscope (TEM) is expected to be a promising technique to screen and identify the different (organic) compounds used in a typical pharmaceutical or biological system and to detect any impurities present, if any, during the synthesis or formulation process. In this work, we propose the use of monochromated TEM-EELS, to analyze selected peptides and organic compounds and their polymorphs. In order to validate EELS for fingerprinting (in low loss/optical region) and by further correlation with advanced DFT, simulations were utilized.
有机化合物和生物化合物（尤其是那些与制药行业相关的化合物）一直是研究人员极为感兴趣的对象，因为它们对于开发用于诊断、治愈、治疗或预防疾病的新药至关重要。由于许多新的活性药物成分（API）及其多晶型物以纳米晶体或无定形形式与无定形聚合物基质混合（称为无定形固体分散体-ASD），使用传统的X射线/拉曼/红外技术在纳米尺度上对其进行结构鉴定和表征变得困难。在任何API合成/生产过程中或在制剂药品中，都必须对杂质进行鉴定和表征。通过透射电子显微镜（TEM）以高能量分辨率进行的电子能量损失谱（EELS）有望成为一种有前景的技术，用于筛选和鉴定典型制药或生物系统中使用的不同（有机）化合物，并检测合成或制剂过程中存在的任何杂质（如果有的话）。在这项工作中，我们提议使用单色化TEM-EELS来分析选定的肽和有机化合物及其多晶型物。为了验证EELS用于指纹识别（在低损失/光学区域）并通过与先进的密度泛函理论（DFT）进一步关联，我们进行了模拟。
