Determination of relative response factors for chromatographic investigations using NMR spectrometry

In the absence of suitable reference materials for impurity quantitation, laboratories have developed techniques using mass detectors such as the chemical luminescence detector (CLND) and the charged aerosol detector (CAD) to normalize the UV response of each impurity of interest by their molar ratios and thus generate relative response factors without requiring isolated and purified compound-specific standards. While effective, these detectors are limited in response and are effective only with specific mobile phase requirements. Nuclear magnetic resonance (NMR) spectrometry has the advantage of allowing the universal detection of protons while not suffering from the limitations observed for CLND, CAD, and other common detectors. The determination of relative response factors using NMR has been successfully applied to several LC methods. An overview of this technique and representative results are presented.