Quantifying Hydrogen Populations in Liquid Mixtures Using ¹H NMR Relaxometry.

Area of Science:

• Analytical Chemistry
• Materials Science
• Pharmaceutical Science

Background:

• Liquid mixtures, particularly pharmaceutical products, require precise quantification of components for quality assurance.
• Traditional analytical methods can be time-consuming and may not fully capture the dynamic nature of liquid mixtures.

Purpose of the Study:

• To quantify hydrogen population fractions in liquid mixtures, including pharmaceutical formulations, using time-domain ¹H NMR relaxometry.
• To assess the accuracy and speed of ¹H NMR relaxometry for determining ingredient composition in drug products.
• To explore the potential of ¹H NMR relaxometry for verifying content uniformity in liquid drug products.

Main Methods:

• Utilized time-domain proton nuclear magnetic resonance (¹H NMR) relaxometry to measure transverse relaxation rates (R₂(¹H)) of different hydrogen populations.
• Applied the distinct R₂(¹H) values to differentiate and quantify hydrogen fractions in various liquid mixtures.
• Analyzed eight diverse drug products, including five emulsions and three solutions.

Main Results:

• ¹H NMR relaxometry successfully quantified hydrogen population fractions in liquid mixtures within one minute.
• For drug products with two dominant ingredients, the method provided accurate quantification of hydrogen fractions.
• Discrepancies between NMR-derived fractions and chemically calculated values were minimal (<2% for seven products, 6% for one).

Conclusions:

• Time-domain ¹H NMR relaxometry is a rapid and accurate technique for quantifying hydrogen population fractions in liquid mixtures.
• This NMR approach offers a reliable method for assessing the composition and content uniformity of liquid drug products.
• The technique holds promise for routine quality control and batch release testing in the pharmaceutical industry.