Solid-State NMR Studies of Form I of Atorvastatin Calcium

Solid-state 13C, 19F, and 15N magic angle spinning NMR studies of Form I of atorvastatin calcium are reported, including chemical shift tensors of all resolvable carbon sites and fluorine sites. The complete 13C and 19F chemical shift assignments are given based on an extensive analysis of 13C–1H HETCOR and 13C–19F HETCOR results. The solid-state NMR data indicate that the asymmetric unit of this material contains two atorvastatin molecules. A possible structure of Form I of atorvastatin calcium (ATC-I), derived from solid-state NMR data and density functional theory calculations of various structures, is proposed for this important active pharmaceutical ingredient (API).本研究报道了阿托伐他汀钙（atorvastatin calcium）晶型I的固态13C、19F及15N魔角旋转核磁共振（Magic Angle Spinning NMR）研究结果，涵盖所有可分辨碳位点与氟位点的化学位移张量。基于对13C–1H异核相关谱（Heteronuclear Correlation Spectroscopy, HETCOR）与13C–19F异核相关谱结果的详尽分析，本文完成了13C与19F化学位移的全部归属。固态核磁共振数据表明，该物质的不对称结构单元包含两个阿托伐他汀分子。针对这一重要的药用活性成分（Active Pharmaceutical Ingredient, API），本文基于固态核磁共振数据与多种结构的密度泛函理论（Density Functional Theory, DFT）计算结果，提出了阿托伐他汀钙晶型I（ATC-I）的可能结构。