High-throughput differentiation of heparin from other glycosaminoglycans by pyrolysis mass spectrometry
Research article published in Analytical chemistry (2013)
Abstract
Sensors with high chemical specificity and enhanced sample throughput are vital to screening food products and medical devices for chemical or biochemical contaminants that may pose a threat to public health. For example, the rapid detection of oversulfated chondroitin sulfate (OSCS) in heparin could prevent reoccurrence of heparin adulteration that caused hundreds of severe adverse events including deaths worldwide in 2007-2008. Here, rapid pyrolysis is integrated with direct analysis in real time (DART) mass spectrometry to rapidly screen major glycosaminoglycans, including heparin, chondroitin sulfate A, dermatan sulfate, and OSCS. The results demonstrate that, compared to traditional liquid chromatography-based analyses, pyrolysis mass spectrometry achieved at least 250-fold higher sample throughput and was compatible with samples volume-limited to about 300 nL. Pyrolysis yielded an abundance of fragment ions (e.g., 150 different m/z species), many of which were specific to the parent compound. Using multivariate and statistical data analysis models, these data enabled facile differentiation of the glycosaminoglycans with high throughput. After method development was completed, authentically contaminated samples obtained during the heparin crisis by the FDA were analyzed in a blinded manner for OSCS contamination. The lower limit of differentiation and detection were 0.1% (w/w) OSCS in heparin and 100 ng/μL (20 ng) OSCS in water, respectively. For quantitative purposes the linear dynamic range spanned approximately 3 orders of magnitude. Moreover, this chemical readout was successfully employed to find clues in the manufacturing history of the heparin samples that can be used for surveillance purposes. The presented technology and data analysis protocols are anticipated to be readily adaptable to other chemical and biochemical agents and volume-limited samples.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Sensors with high chemical specificity and enhanced sample throughput are vital to screening food products and medical devices for chemical or biochemical contaminants that may pose a threat to public health.
Warum dies für die Hirudotherapie relevant ist
This study examined a rapid pyrolysis and direct analysis in real-time mass spectrometry method to differentiate heparin from other glycosaminoglycans and screen for contaminants like oversulfated chondroitin sulfate. While heparin is a well-known anticoagulant relevant to the broader medical field, this work focuses entirely on pharmaceutical quality control and assay development for a mammalian-derived drug with high sample throughput. The research has absolutely no involvement of leeches or their therapeutic secretomes. Therefore, its relevance to the American Society of Hirudotherapy is entirely absent, serving strictly as an indirect discussion of anticoagulant safety surveillance.
Zitation
High-throughput differentiation of heparin from other glycosaminoglycans by pyrolysis mass spectrometry
Nemes P et al. · Analytical chemistry, 2013
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