Quantifying Hydrogen Populations in Liquid Mixtures Using 1H NMR Relaxometry

The fractions of hydrogen populations in various liquid mixtures, including liquid drug products, were quantified using time-domain ¹H NMR relaxometry. Different hydrogens in a liquid mixture have different ¹H transverse relaxation rates R₂(¹H), forming the basis for quantification. For drug products that contain two dominant ingredients (the solvent and the solute, with or without minor ingredients), ¹H NMR relaxometry can quantify the two ingredients in the form of hydrogen population fractions within 1 min. For the eight drug products tested in this study, including five emulsions and three solutions, the discrepancy between hydrogen fractions from NMR and those calculated from chemical composition is less than 2% for seven products and 6% for one product. ¹H NMR relaxometry may be used to verify the content uniformity of a liquid drug product by quantifying the hydrogen populations within individual vials in the batch.