Determination of Analyte Concentration Using the Residual Solvent Resonance in ¹H NMR Spectroscopy

Abstract

An NMR protocol that uses the residual proton signal from DMSO -d(6) (i.e., DMSO -d(5)) to determine the concentration of an analyte in a NMR sample was developed. This technique provides an alternative method for determining the molar concentration of compounds in solution without prior knowledge of their molecular weight. The method is particularly useful when submilligram quantities of compound are to be analyzed and is applicable to a variety of different research areas such as compound management, and natural product, combinatorial, and medicinal chemistry.

Evolution of Quantitative Measures in NMR: Quantum Mechanical qHNMR Advances Chemical Standardization of a Red Clover (Trifolium pratense) Extract

“…Additionally, an EC can be used to calibrate the (residual) solvent signal, which can then be used as an IC for an extended series of qHNMR analyses (ECIC method), 31 provided the same batch of solvent is used throughout and the exact volume is known. Traditionally, these quantitation modes have employed manual integration of the NMR signals as a quantitative measure.…”

Quantitative NMR Studies of Multiple Compound Mixtures

“…Besides using internal or external standards, the 1 H NMR signals from the residual protonated fraction of a deuterated solvent can also be exploited as an internal standard provided that the residual protonated fraction is quantified accurately [36]. Quantification by NMR can also be determined by reference to a synthesized electronic signal using the ERETIC technique (electronic reference to assess in vivo concentrations) [37].…”

Expanding the Analytical Toolbox: Pharmaceutical Application of Quantitative NMR

“…25,26 Several natural products have been analyzed using residual solvents as the internal standards. 27 The use of residual solvents has an advantage of keeping the sample clean in case it needs to be retrieved. On the other hand, the amount of residual solvent varies from bottle to bottle and from batch to batch.…”