Quantitative nuclear magnetic resonance of chloride by an accurate internal standard approach |
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Authors: | Jared S Wood Guilherme Dal Poggetto Xiao Wang Mikhail Reibarkh R Thomas Williamson Ryan D Cohen |
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Institution: | 1. Merck & Co., Inc., Rahway, New Jersey, USA;2. Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina, USA |
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Abstract: | Chloride is the most common counterion used to improve aqueous solubility and enhance stability of small molecule active pharmaceutical ingredients. While several analytical techniques, such as titration, HPLC with charged aerosol detection, and ion chromatography, are currently utilized to assay the level of chloride, they have notable limitations, and these instruments may not be readily available. Here, we present a generally applicable 35Cl solution NMR method to assay the level of chloride in pharmaceutical compounds. The method uses KClO4 as an internal standard for improved accuracy in comparison with external standard methods, and it was found to be robust, linear over three orders of magnitude, precise (<3% RSD), and accurate (<0.5% absolute error). |
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Keywords: | 35Cl counterions pharmaceuticals quadrupolar quantitative NMR |
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