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Pentosan Polysulfate Sodium Profiling with Mass Spectrometry


EMSL Project ID
60655

Abstract

PPS is a semisynthetic heterogeneous sulfated polysaccharide derived from xylan, the β-1,4-linked polymer of xylose that is the backbone structural component of hemicellulose in most types of wood and other fibrous plants. PPS is the active ingredient in the drug product formulation known by the brand name Elmiron in the US, where it is used to treat interstitial cystitis (IC), a condition of the epithelial lining of the bladder that manifests as bladder or pelvic pain and discomfort. PPS is produced by extracting xylan from plant matter (often beechwood), chemically modifying the xylan to form sulfate esters at the free hydroxyl groups, and fragmenting the sulfated xylan into lower molecular weight oligosaccharides. PPS contains scattered modifications including 2-(α-1-(4-O-methyl)-glucuronic acid), residual O-acetylation following alkaline extraction of hemicellulose from wood, and partial pyridinylation from the sulfation reaction at the reducing end of the xylan. Variations in the degree of sulfation and the length of the oligosaccharide add additional complexity to create mixtures that contain hundreds or more different species. The range of masses and chemical speciation in PPS affords a heterogenous mixture of molecular species whose characterization and profiling present a considerable challenge to demonstration of physicochemical similarity. The goal of this study is to detect and profile PPS (and metabolites, if any) in plasma and urine, and comparing these profiles to that of the ingested PPS to assess bioequivalence among different sources of PPS.

Project Details

Start Date
2023-01-25
End Date
2023-10-01
Status
Closed

Team

Principal Investigator

John Cort
Institution
Pacific Northwest National Laboratory

Team Members

Madelyn Berger
Institution
Pacific Northwest National Laboratory

John Melchior
Institution
Pacific Northwest National Laboratory

Robert Gerbasi
Institution
Pacific Northwest National Laboratory

Chaevien Clendinen
Institution
Environmental Molecular Sciences Laboratory

Isaac Attah
Institution
Pacific Northwest National Laboratory

Heather Olson
Institution
Environmental Molecular Sciences Laboratory