Analytical Research & Development, Merck & Co., Inc., Rahway, NJ 07065, USA.
Bruker Biospin Corporation, Billerica, MA 01821, USA.
Analyst. 2023 Feb 13;148(4):724-734. doi: 10.1039/d2an01903e.
Solid-state nuclear magnetic resonance (ssNMR) is a high-resolution and versatile spectroscopic tool for characterizing pharmaceutical solids. However, the inherent low sensitivity of NMR remains a significant challenge in the analysis of natural abundance drug substances and products. Here, we report, for the first time, the application of a CPMAS CryoProbe™ to improve the sensitivity of C and N detection by approximately 5 to 6 times for solid-state analysis of a commercial pharmaceutical drug posaconazole (POSA). The sensitivity enhancement enables two-dimensional (2D) C-C and H-N correlation experiments, which are otherwise time-prohibitive using regular MAS probes, for resonance assignment and structural elucidation. These polarization transfer and correlation experiments reveal drug-drug and drug-polymer interactions in amorphous POSA and its amorphous solid dispersion formulation. Our results demonstrated that the CPMAS CryoProbe™ can be widely applied for routine pharmaceutical analysis and advanced structural investigations with significantly enhanced efficiency and throughput.
固态核磁共振（ssNMR）是一种用于表征药物固体的高分辨率、多功能的光谱学工具。然而，NMR 固有的低灵敏度仍然是分析天然丰度药物物质和产品的一个重大挑战。在这里，我们首次报道了 CPMAS CryoProbe™的应用，该应用可将固态分析商业药物泊沙康唑（POSA）时 C 和 N 的检测灵敏度提高约 5 到 6 倍。灵敏度的提高使二维（2D）C-C 和 H-N 相关实验成为可能，否则使用常规 MAS 探头进行这些实验则需要耗费大量时间。这些极化转移和相关实验揭示了无定形 POSA 及其无定形固体分散体配方中的药物-药物和药物-聚合物相互作用。我们的结果表明，CPMAS CryoProbe™可广泛应用于常规药物分析和高级结构研究，显著提高效率和通量。
