Pharmaceutical analysis by NMR can accommodate strict impurity thresholds: The case of choline

Quantum-Mechanical Driven 1H Iterative Full Spin Analysis Addresses Complex Peak Patterns of Choline Sulfate

“…Choline and choline phosphate were also subjected to the QM-HiFSA process (S3 for choline and S4 for choline phosphate in the Supporting Information) for comparative interpretation. The QM-HiFSA profile of choline in this study was in good agreement with a recent computational study of the 1 H NMR spectrum of choline . The full spin analysis of choline phosphate yielded chemical shift and coupling constant values comparable to that from a previous spectral optimization and simulation, but significant progress was made in the present study, involving small 1 H– 14 N and 1 H– 31 P couplings.…”

“…The QM-HiFSA profile of choline in this study was in good agreement with a recent computational study of the 1 H NMR spectrum of choline. 15 The full spin analysis of choline phosphate yielded chemical shift and coupling constant values comparable to that from a previous spectral optimization and simulation, 16 but significant progress was made in the present study, involving small 1 H– 14 N and 1 H– 31 P couplings. Moreover, the present analysis provides a systematic understanding of the non-first-order coupling rather than reporting only separate J values as before.…”

“…On the other hand, the value of the three-bond heteronuclear coupling (i.e., 3 J HN and 3 J HP ) is large enough to cause additional peaks in the H 2 -1 resonance pattern. In this regard, previous manual spectral analyses have interpreted the relatively simple H 2 -2 pattern to obtain H-1/H-2 vicinal couplings. , However, recently, computer-assisted spectral analysis has allowed the determination of geminal and vicinal couplings in highly complex H 2 -1 resonance patterns. , The QM-HiFSA in the present study yielded a complete analysis of the geminal ( 2 J HH ) and vicinal 1 H– 1 H couplings ( 3 J HH ) of choline sulfate (Table ): 2 J HH = −13.81 Hz and 3 J HH = 7.16 and 2.12 Hz, respectively. Optimized vicinal coupling values of choline and choline phosphate were also obtained (choline, 3 J HH = 6.89 and 3.16 Hz; choline phosphate, 3 J HH = 6.98 and 2.54 Hz), which were consistent with previously reported values , and also comparable to those of choline sulfate.…”

“…20,24 However, recently, computer-assisted spectral analysis has allowed the determination of geminal and vicinal couplings in highly complex H 2 -1 resonance patterns. 15,16 The QM-HiFSA in the present study yielded a complete analysis of the geminal ( 2 J HH ) and vicinal 1 H− 1 H couplings ( 3 J HH ) of choline sulfate (Table 1): 2 J HH = −13.81 Hz and 3 J HH = 7.16 and 2.12 Hz, respectively. Optimized vicinal coupling values of choline and choline phosphate were also obtained (choline, 3 J HH = 6.89 and 3.16 Hz; choline phosphate, 3 J HH = 6.98 and 2.54 Hz), which were consistent with previously reported values 15,16 and also comparable to those of choline sulfate.…”

Elucidating the Structure, Dynamics, and Interaction of a Choline Chloride and Citric Acid Based Eutectic System by Spectroscopic and Molecular Modeling Investigations

“…Meanwhile, other prominent peaks of C−H at 3A, and their proton chemical shifts are consistent with published values. 35,36 TMS (tetramethylsilane) was assigned a chemical shift of zero (0.00 ppm) and was used as the internal reference substance during the dilution 1 H NMR experiment of DESs. To begin the experiment, a 1 H NMR spectrum of DESs was obtained in DMSO-d 6 (Figure 3B).…”