Abstract：
Protons represent the most NMR-sensitive nucleus in pharmaceutical compounds. Therefore, proton-detected solid-state NMR techniques under fast magic angle spinning are among the few solutions to overcome the challenge of low sensitivity to analyze natural abundant drug substances and products. In this study, we report the structural characterization of crystal polymorphs of a commercial drug molecule, posaconazole, with a relatively large molecular weight of 700.8 g·mol-1 and at the natural abundance. The enhanced sensitivity and resolution at 100 kHz MAS enables the exploration of the distinct intermolecular packing in posaconazole forms I, III, and γ. These results demonstrate that proton-detected homo- and heteronuclear correlation methods can probe the structural details of pharmaceutical polymorphism.
摘要：
质子代表药物化合物中对NMR最敏感的核。因此,快速幻角旋转下的质子检测固态NMR技术是克服分析天然丰富药物和产品的低灵敏度挑战的少数解决方案之一。在这项研究中,我们报道了商业药物分子的晶体多晶型物的结构表征，泊沙康唑,分子量相对较大，为700.8g·mol-1，天然丰度。在100kHzMAS下增强的灵敏度和分辨率可以探索泊沙康唑I型中独特的分子间堆积，III,和γ。这些结果表明，质子检测的同源和异核相关方法可以探测药物多态性的结构细节。
