Science & Research

Mass Spectrometry Profiling of Pentosan Polysulfate in Urine

Principal Investigator: John R. Cort, Ph.D.

Performer: Battelle Memorial Institute (PNNL)

Project Duration: 09/23/2016 – 09/22/2018

Regulatory Science Challenge:

Pentosan polysulfate (PPS) is a semisynthetic heterogeneous polysaccharidederived from xylan, a componentof fibrous plants and many types of wood (usually from the bark of the beech tree). PPS is produced by first chemically extracting xylan from plant matter, then treating xylan with sulfating agents to form sulfate esters, and finally the sulfated xylan is fragmented into oligosaccharides.

PPS is primarily used to treat interstitial cystitis, a condition of the epithelial lining of the bladder that manifests as bladder or pelvic pain and discomfort. It is known that PPS is poorly absorbed when taken orally, with only a small fraction reaching the bladder—most remains in the GI tract and is eventually excreted. Nonetheless, studies have shown—through urine excretion—that periodic daily intake of PPS can lead to a steady state absorption level in the bladder at a level spanning nearly two orders of magnitude.

PPS is excreted in the urine, which makes analysis and characterization of PPS in urine a valid means of assessing bioequivalence between generic and reference PPS drugs. This study aims to develop a method that incorporates three analytical techniques: solid-phase extraction, ion-mobility spectrometry, and mass spectrometry, hereafter being referred as SPE-IMS-MS, for high throughput (HTP) profiling of PPS in urine. The idea is to eventually use this HTP method to establish bioequivalence of PPS from alternative sources based on its profile in urine. If successful, this method will provide the FDA a rapid and low-cost tool for comparing potential generic versions of PPS to the reference drug.

Project Description & Goals:

The researchers proposed to develop and test a method for profiling PPS in urine using SPE-IMS-MS, building on what has been accomplished already to-date for profiling PPS from Elmiron capsules, and extending their infrastructure for HTP urine metabolite analysis to include PPS.

To that end, they will first identify the best method for extraction of PPS from urine. The methods they planned to explore are: liquid-liquid extraction, enzyme treatment, solid-phase extraction, size exclusion chromatography, gel permeation chromatography, liquid chromatography (with varying concentration of samples, salt, and counterions in the column). SPE-IMS-MS analyses will be used to determine extraction efficiency for each method.

Based on the sensitivity and the limit of quantitation, the researchers will then develop a protocol to scale up, streamline, and validate the analyses.

Achievements:

  • Mass Spectrometry Profiling of Pentosan Polysulfate Sodium (External Poster, 65th ASMA Conference on Mass Spectrometry and Allied Topics, April 8, 2017)

 

Page Last Updated: 11/16/2017
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