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Title: Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs

14N ultra-wideline (UW), 1H{ 15N} indirectly-detected HETCOR (idHETCOR) and 15N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of 14N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. Here, a case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes. For most of the APIs, it was possible to acquire frequency-stepped UW 14N SSNMR spectra of stationary samples, which display powder patterns corresponding to pseudo-tetrahedral (i.e., RR'R"NH + and RR'NH 2 +) or other (i.e., RNH 2 and RNO 2) nitrogen environments.
Authors:
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [3] ;  [3] ;  [1]
  1. Univ. of Windsor, Windsor (Canada)
  2. Durham Univ., Durham (United Kingdom)
  3. Ames Lab. and Iowa State Univ., Ames, IA (United States)
Publication Date:
Report Number(s):
IS-J-9006
Journal ID: ISSN 1463-9076; PPCPFQ
Grant/Contract Number:
AC02-07CH11358
Type:
Accepted Manuscript
Journal Name:
Physical Chemistry Chemical Physics. PCCP (Print)
Additional Journal Information:
Journal Name: Physical Chemistry Chemical Physics. PCCP (Print); Journal Volume: 18; Journal Issue: 26; Journal ID: ISSN 1463-9076
Publisher:
Royal Society of Chemistry
Research Org:
Ames Laboratory (AMES), Ames, IA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1278752

Veinberg, Stanislav L., Johnston, Karen E., Jaroszewicz, Michael J., Kispal, Brianna M., Mireault, Christopher R., Kobayashi, Takeshi, Pruski, Marek, and Schurko, Robert W.. Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs. United States: N. p., Web. doi:10.1039/C6CP02855A.
Veinberg, Stanislav L., Johnston, Karen E., Jaroszewicz, Michael J., Kispal, Brianna M., Mireault, Christopher R., Kobayashi, Takeshi, Pruski, Marek, & Schurko, Robert W.. Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs. United States. doi:10.1039/C6CP02855A.
Veinberg, Stanislav L., Johnston, Karen E., Jaroszewicz, Michael J., Kispal, Brianna M., Mireault, Christopher R., Kobayashi, Takeshi, Pruski, Marek, and Schurko, Robert W.. 2016. "Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs". United States. doi:10.1039/C6CP02855A. https://www.osti.gov/servlets/purl/1278752.
@article{osti_1278752,
title = {Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs},
author = {Veinberg, Stanislav L. and Johnston, Karen E. and Jaroszewicz, Michael J. and Kispal, Brianna M. and Mireault, Christopher R. and Kobayashi, Takeshi and Pruski, Marek and Schurko, Robert W.},
abstractNote = {14N ultra-wideline (UW), 1H{15N} indirectly-detected HETCOR (idHETCOR) and 15N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of 14N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. Here, a case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes. For most of the APIs, it was possible to acquire frequency-stepped UW 14N SSNMR spectra of stationary samples, which display powder patterns corresponding to pseudo-tetrahedral (i.e., RR'R"NH+ and RR'NH2+) or other (i.e., RNH2 and RNO2) nitrogen environments.},
doi = {10.1039/C6CP02855A},
journal = {Physical Chemistry Chemical Physics. PCCP (Print)},
number = 26,
volume = 18,
place = {United States},
year = {2016},
month = {6}
}