In-depth structural characterization of pentosan polysulfate sodium complex drug using orthogonal analytical tools

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Polymer Chemistry

Background:

• Characterizing complex drug active ingredients like pentosan polysulfate (PPS) requires advanced analytical technologies.
• Pentosan polysulfate (PPS) is a heterogeneous sulfated polysaccharide used in Elmiron® for interstitial cystitis treatment.
• Defining critical quality attributes (CQAs) for such complex drugs necessitates integrated analytical strategies.

Purpose of the Study:

• To develop and validate an integrated analytical approach for characterizing the complex active ingredient pentosan polysulfate (PPS).
• To establish a framework for defining critical quality attributes (CQAs) of heterogeneous polysaccharides like PPS.
• To enable scientifically sound comparative characterization of drug products containing complex active ingredients.

Main Methods:

• Integration of orthogonal analytical methodologies.
• Utilized gel permeation chromatography (GPC) for size characterization.
• Employed liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) and nuclear magnetic resonance (NMR) for structural and compositional analysis.

Main Results:

• Developed a novel mathematical framework to integrate data from diverse analytical methods.
• The framework relates analytical data to PPS chain length and building block composition.
• Successfully measured critical quality attributes (CQAs) of pentosan polysulfate (PPS).

Conclusions:

• The integrated analytical approach provides a robust method for characterizing complex polysaccharides like PPS.
• This framework facilitates the establishment of a scientific basis for comparative drug product analysis.
• Advances analytical capabilities for ensuring the quality of complex pharmaceutical ingredients.