Review of Advances in Quantitative Nuclear Magnetic Resonance Methods for Removing Impurity Interference
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Graphical Abstract
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Abstract
Quantitative nuclear magnetic resonance (qNMR) is a potential primary method for determining the purity of organic compounds, which can establish the metrological traceability of the vast majority of organic compounds. The principles, advantages, and challenges of the recent approaches of qNMR methods that can effectively separate the impurity peaks from the quantitative peaks of the analytes are reviewed, including the combination of high-performance liquid chromatography (HPLC) and qNMR, HPLC-qNMR with bi-deuterated mobile phase, HPLC-single-signal-suppression qNMR with single-deuterated mobile phase, HPLC-double-signal-suppression qNMR, internal standard recovery correction (ISRC)-HPLC-qNMR, internal standard correction(ISC)-HPLC-qNMR, extended internal standard method for qNMR assisted by chromatography (EIC), peptide impurity corrected qNMR (PICqNMR), two-dimensional NMR: quantitative heteronuclear single quantum correlation NMR (qHSQC), and HPLC-qNMR-HPLC. These methods can reduce the potential systematic errors in qNMR, improve the accuracy of the results, and expand the application of qNMR as a metrological potential primary method and a routine analysis method.
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