Quantitative measurement of Toll-like receptor 4 agonists adsorbed to Alhydrogel(®) by Fourier transform infrared-attenuated total reflectance spectroscopy

• Published in: Journal of pharmaceutical sciences Vol. 104; no. 2; p. 768
• Main Authors: Dowling, Quinton M, Schwartz, Alicia M, Vedvick, Thomas S, Fox, Christopher B, Kramer, Ryan M
• Format: Journal Article
• Language: English
• Published: United States 01-02-2015
• Subjects: Adsorption; Aluminum Hydroxide - analysis; Aluminum Hydroxide - metabolism; Glucosides - analysis; Glucosides - metabolism; Lipid A - analysis; Lipid A - metabolism; Spectroscopy, Fourier Transform Infrared - methods; Toll-Like Receptor 4 - agonists; adsorption; glucopyranosyl lipid adjuvant (GLA); vaccines; FTIR; hydrogels; aluminum hydroxide adjuvant; Absorption Spectroscopy; vaccine adjuvants
• ISSN: 1520-6017
• DOI: 10.1002/jps.24180

Aluminum salts have a long history as safe and effective vaccine adjuvants. In addition, aluminum salts have high adsorptive capacities for vaccine antigens and adjuvant molecules, for example, Toll-like receptor 4 (TLR4) agonists. However, the physicochemical properties of aluminum salts make direct quantitation of adsorbed molecules challenging. Typical methods for quantifying adsorbed molecules require advanced instrumentation, extreme sample processing, often destroy the sample, or rely on an indirect measurement. A simple, direct, and quantitative method for analysis of adsorbed adjuvant molecules is needed. This report presents a method utilizing Fourier transform infrared spectroscopy with a ZnSe-attenuated total reflectance attachment to directly measure low levels (<30 μg/mL) of TLR4 agonists adsorbed on aluminum salts with minimal sample preparation.