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

Abstract

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:
Research Org.:
Ames Laboratory (AMES), Ames, IA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1278752
Report Number(s):
IS-J-9006
Journal ID: ISSN 1463-9076; PPCPFQ
Grant/Contract Number:  
AC02-07CH11358
Resource Type:
Journal Article: 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
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

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., 2016. 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.. Wed . "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 = {Wed Jun 08 00:00:00 EDT 2016},
month = {Wed Jun 08 00:00:00 EDT 2016}
}

Journal Article:
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Cited by: 11 works
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