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Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders
11:14

Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders

Published on: April 14, 2015

Determination of residual moisture in lyophilized protein pharmaceuticals using a rapid and non-invasive method: near

Tanya P Lin1, Chung C Hsu

  • 1Genentech, Inc., Dept. of Pharmaceutical R&D, 1 DNA Way, South San Francisco, CA 94080, USA. tmoy@gene.com

PDA Journal of Pharmaceutical Science and Technology
|August 17, 2002
PubMed

Insights

Near-infrared (NIR) spectroscopy accurately measures residual moisture in lyophilized pharmaceuticals, matching Karl Fischer titration precision. Formulation changes, especially disaccharide levels, impact accuracy, highlighting the need for consistent lyoprotectant concentrations for reliable moisture analysis.

Area of Science:

  • Analytical Chemistry
  • Pharmaceutical Sciences
  • Spectroscopy

Background:

  • Accurate residual moisture determination is critical for lyophilized protein pharmaceutical stability.
  • Karl Fischer titration is a standard method, but alternative techniques are sought for non-destructive analysis.
  • Near-infrared (NIR) spectroscopy offers potential for rapid, in-situ moisture assessment.

Purpose of the Study:

  • To evaluate the efficacy of near-infrared (NIR) spectroscopy for quantifying residual moisture in lyophilized protein pharmaceuticals.
  • To assess the impact of formulation variables and product configuration on NIR measurement accuracy.
  • To explore NIR spectroscopy's potential for evaluating the solid-state structure of proteins.

Main Methods:

  • Comparison of NIR spectroscopy with Karl Fischer titration for residual moisture analysis in five pharmaceutical products.
  • Investigation of formulation effects (buffer, surfactant, disaccharide concentrations) on NIR accuracy using a model lyophilized monoclonal antibody.
  • Analysis of lyophilized cake morphology (porosity, dimensions) and its influence on NIR penetration depth.

Main Results:

  • NIR spectroscopy demonstrated comparable precision to Karl Fischer titration for residual moisture determination.
  • Lyophilized cake porosity and dimensions did not affect NIR measurements when exceeding NIR penetration depth.
  • Disaccharide concentration significantly impacted NIR accuracy due to spectral overlap; its complete removal altered protein NIR spectra.

Conclusions:

  • NIR spectroscopy is a viable, precise method for analyzing residual moisture in lyophilized protein pharmaceuticals.
  • Accurate moisture determination by NIR requires consistent lyoprotectant (disaccharide) concentrations to avoid spectral interferences.
  • NIR spectroscopy shows promise for simultaneously assessing moisture content and solid-state protein structure.

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