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Band‐selective excitation NMR spectroscopy and quantitative time‐domain analysis using Complete Reduction to Amplitude‐Frequency Table (CRAFT) to determine distribution coefficients during drug development
Author(s) -
Soulsby David
Publication year - 2019
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.4888
Subject(s) - chemistry , excitation , amplitude , analytical chemistry (journal) , spectroscopy , nuclear magnetic resonance spectroscopy , partition coefficient , distribution (mathematics) , frequency domain , nuclear magnetic resonance , chromatography , stereochemistry , optics , mathematical analysis , physics , mathematics , quantum mechanics
Abstract A sensitive quantitative 1 H NMR method for determining distribution or partition coefficients has been developed that is applicable to early drug discovery. After partitioning and equilibration, aliquots from each layer are analyzed using band‐selective excitation 1 H NMR spectroscopy in regions that are free of 1‐octanol and water solvent signals. Signals are quantitated directly using CRAFT software, and their amplitudes are adjusted to correct for nonuniformity within the excitation band. Using this approach, the distribution coefficients for 20 drugs present at low concentrations were determined giving values that were in excellent agreement with literature values.