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In response to the changing market pressures being applied to the pharmaceutical industry, a greater emphasis is being made to advance new drugs to market with minimal investment in early development stages. The use of quantitative NMR (q-NMR) has been shown to be a single point replacement for routine early development testing which previously combined elements of identity testing, chromatographic assay, moisture analysis, residual solvent analysis, and elemental analysis. This Feature will highlight the applications of q-NMR to early phase drug development testing and its efficient potency, solvent quantification, and relative response factor determinations.

With the changing development paradigms in the pharmaceutical industry, laboratories are challenged to release materials for clinical studies with rapid turnaround times. To minimize cost demands, many businesses are looking to develop ways of using early Good Manufacturing Practice (GMP) materials of active pharmaceutical ingredients (API) for Good Laboratory Practice (GLP) toxicology studies. To make this happen, the analytical laboratory releases the material by one of three scenarios: (1) holding the GLP release until full GMP testing is ready, (2) issuing a separate lot number for a portion of the GMP material and releasing the material for GLP use, or (3) releasing the lot of material for GLP using alternate (equivalent) method(s) not specified for GMP release testing. Many companies are finding the third scenario to be advantageous in terms of cost and efficiency through the use of quantitative nuclear magnetic resonance (q-NMR). The use of q-NMR has proved to be a single-point replacement for routine early development testing that previously combined elements of identity testing, chromatographic assay, moisture analysis, residual solvent analysis, and elemental analysis. This study highlights that q-NMR can be validated to meet current regulatory analytical method guidelines for routine pharmaceutical analysis.

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.