27Al and 31P NMR spectroscopy method development to quantify aluminum phosphate in adjuvanted vaccine formulations.

A novel qNMR method is described for the quantitative determination of total aluminum and phosphate in aluminum phosphate (AlPO4) adjuvanted vaccine samples using solution 27Al and 31P nuclear magnetic resonance (NMR) spectroscopy. External standard calibrations of AlPO4 solutions established excellent linearity in the range of 15-40 × 10-3 M and additional studies determined the level of detection for both nuclei. A commercialized combination vaccine product (Quadracel®), along with several individual adsorbed antigen components used in the vaccine were employed as model systems for method development. The developed method is also capable of quantitating the free phosphate (i.e. the fraction not bound to AlPO4 particles) in adjuvanted vaccines. This study is the first demonstration of a solution NMR method that is suitable for measuring total aluminum, and free and total phosphate concentrations in vaccine formulations consisting of antigen(s) adsorbed to aluminum adjuvant, in a single analytical workflow.