Method to detect contaminants in heparin using radical depolymerization and liquid chromatography-mass spectrometry.

Area of Science:

• Pharmaceutical Chemistry
• Analytical Chemistry
• Biochemistry

Background:

• Heparin, a vital anticoagulant, was implicated in severe adverse events in 2008 due to contamination.
• The exact nature of the 2008 contaminant remains debated, with potential for new adulterants like N-sulfo oversulfated chondroitin sulfate.

Purpose of the Study:

• To synthesize N-sulfo oversulfated chondroitin sulfate, a potential new heparin contaminant.
• To develop and apply analytical methods for detecting this new contaminant in heparin.
• To confirm the structure of the 2008 heparin contaminant.

Main Methods:

• Synthesis of N-sulfo oversulfated chondroitin sulfate.
• Radical depolymerization for sample preparation.
• Liquid chromatography-mass spectrometry (LC-MS) for detection and structural elucidation.

Main Results:

• Successful synthesis of N-sulfo oversulfated chondroitin sulfate.
• Development of a method to detect N-sulfo oversulfated chondroitin sulfate in heparin samples.
• Confirmation that the 2008 heparin contaminant was oversulfated chondroitin sulfate, not oversulfated heparan sulfate.

Conclusions:

• Heparin adulteration with N-sulfo oversulfated chondroitin sulfate is a plausible concern.
• Radical depolymerization coupled with LC-MS is effective for detecting and characterizing heparin contaminants.
• Accurate identification of heparin contaminants is crucial for patient safety and regulatory oversight.