Structure elucidation capabilities on typical pharmaceutical drugs by new nuclear magnetic resonance technology: a 400 MHz high-temperature superconducting power-driven magnet NMR system

• Published in: Instrumentation science & technology 2019-03, Vol.47 (2), p.195-212
• Main Authors: Silva Elipe, Maria Victoria, Donovan, Neil, Krull, Robert, Pooke, Donald, Colson, Kimberly L.
• Format: Article
• Language: English
• Subjects: Broadband; Carbon 13; Excitation; Experiments; Fluorine; High temperature; Molecular structure; New technology; NMR; Nuclear magnetic resonance; Organic chemistry; Pharmaceutical industry; Pharmaceuticals; Probes; Superconductivity
• ISSN: 1073-9149; 1525-6030
• DOI: 10.1080/10739149.2018.1516226

Nuclear magnetic resonance (NMR) is a powerful technique for the structure elucidation of organic molecules and significantly important in the pharmaceutical industry supporting the discovery and development of drug substances or active pharmaceutical ingredients (APIs). Following an initial study and assessment of a prototype NMR instrument with a high-temperature superconducting (HTS) power-driven magnet of 9.4 T (400 MHz for 1H observation) operating with standard commercial electronics and probes, we tested the instrument with three compounds representing typical pharmaceutical drugs. We compared results from two probes and shimstacks with different geometries (broadband fluorine observe (BBFO) with Bruker orthogonal shim system-3 (BOSS3) and Bruker quattro nucleus probe (QNP) with BOSS1 shims) testing standard one-dimensional (1D) NMR experiments including selective excitation experiments, and two-dimensional (2D) homonuclear and heteronuclear experiments for the purposes of evaluating the equipment for structure elucidation capabilities. In our initial study on cinacalcet HCl, only the 1D 1H experiment showed a loss of resolution when using the longer coiled BBFO probe with the BOSS3 shims compared to the shorter coiled QNP probe with BOSS1 shims. The selective excitation experiments using the cinacalcet HCl were successful. Our characterization of 1D (1H, 13C, 19F) and 2D (1H-1H and 1H-13C) NMR experiments for compounds I and II with the two probes and shimstacks indicated no significance differences. Overall, these results are satisfactory with the HTS magnet at the field of 9.4 T for the structural elucidation work of standard pharmaceutical compounds. This new technology has the advantage of being able to locate the HTS NMR magnet system in any chemistry or analytical laboratory where the samples are produced, facilitating rapid analysis with minor needs from the facilities and without cryogenic liquids.