Quantitative NMR Spectroscopy in Pharmaceutical R&D

NMR spectroscopy is famous for structure elucidation of small and large molecules, such as peptides and small proteins. NMR can also be used for quantitative purposes, e. g., the determination of the content of a drug and of its low-level impurities. This is because the area of a signal is proportional to the number of nuclei giving rise to it. A prerequisite for quantification is a pure signal, i. e., no overlap with signals of the same or other compounds. Even though the chemical shift of an atom is mainly determined by its neighboring atoms, a signal can be moved using different solvents, different concentrations, and by means of shift reagents for signal separation. For quantification purposes, the acquisition and processing parameters have to be set carefully. Special attention has to be paid to the complete T-1 relaxation. Quantification can be achieved by means of relative or absolute methods, using either internal or external standards.