The development and qualification of liquid adsorption chromatography for poloxamer 188 characterization

Poloxamer 188 (P188) is formulated in proteinaceous therapeutics as an alternative surfactant to polysorbate because of its good chemical stability and surfactant properties, which enable interfacial protection, preventing visible and sub-visible particle formation. However, due to the nature of polymer heterogeneity and limited analytical approaches to resolve the superimposed components of P188, the impact of its quality variance on protein stability is still not well understood.

Highlights

Liquid adsorption chromatography (LAC) is developed to resolve superimposed components of poloxamer 188 (P188).

The LAC method is reliable for routine P188 quality control.

The LAC enables the establishment of control strategy of P188 in the future.

In this study, we developed an analytical method to evaluate the components of P188 as a function of the length of polypropylene oxide (PPO), by maintaining polyethylene oxide (PEO) at the critical point of adsorption (CPA) to eliminate its chromatographic interference. The effectiveness of the separation was confirmed by nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy (MS) of the individual fractions corresponding to each peak. Additionally, a design of experiments (DoE) and method qualification were carried out to identify and optimize the key operation parameters, including column temperature and evaporative light scattering detector (ELSD) settings that need to be strictly controlled for reliable analytical results.

In conclusion, this method is sensitive and reliable to compare the quality variance of commercial P188 and is suitable for routine quality control purposes. The application of this method could help in further understanding the Critical Material Attributes (CMA) that may affect the quality attributes of proteins in formulations.

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Article information: Wei Chen, Alfred Ross, Bernd Steinhuber, Gabriel Hoffmann, Nuria Sancho Oltra, Satya Krishna Kishore Ravuri, Steven Bond, Christian Bell, Robert Kopf. The development and qualification of liquid adsorption chromatography for poloxamer 188 characterization, Journal of Chromatography A, Volume 1652, 2021. https://doi.org/10.1016/j.chroma.2021.462353.