A robust method to quantify low molecular weight contaminants in heparin: detection of tris(2-n-butoxyethyl) phosphate

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dc.contributor.authorSassaki, Guilherme L.
dc.contributor.authorRiter, Daniel S.
dc.contributor.authorSantana Filho, Arquimedes P.
dc.contributor.authorGuerrini, Marco
dc.contributor.authorLima, Marcelo A. [UNIFESP]
dc.contributor.authorCosentino, Cesare
dc.contributor.authorSouza, Lauro M.
dc.contributor.authorCipriani, Thales R.
dc.contributor.authorRudd, Timothy R.
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorYates, Edwin A.
dc.contributor.authorGorin, Philip A. J.
dc.contributor.authorTorri, Giangiacomo
dc.contributor.authorIacomini, Marcello
dc.contributor.institutionUniv Fed Parana
dc.contributor.institutionIst Ric Chim & Biochim G Ronzoni
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Liverpool
dc.date.accessioned2016-01-24T14:06:00Z
dc.date.available2016-01-24T14:06:00Z
dc.date.issued2011-01-01
dc.description.abstractRecently, oversulfated chondroitin sulfate (OSCS) was identified in contaminated heparin preparations, which were linked to several adverse clinical events and deaths. Orthogonal analytical techniques, namely nuclear magnetic resonance (NMR) and capillary electrophoresis (CE), have since been applied by several authors for the evaluation of heparin purity and safety. NMR identification and quantification of residual solvents and non-volatile low molecular contaminants with USP acceptance levels of toxicity was achieved 40-fold faster than the traditional GC-headspace technique, which takes similar to 120 min against similar to 3 min to obtain a (1)H NMR spectrum with a signal/noise ratio of at least 1000/1. the procedure allowed detection of Class 1 residual solvents at 2 ppm and quantification was possible above 10 ppm. 2D NMR techniques (edited-HSQC (1)H/(13)C) permitted visualization of otherwise masked EDTA signals at 3.68/59.7 ppm and 3.34/53.5 ppm, which may be overlapping mononuclear heparin signals, or those of ethanol and methanol. Detailed NMR and ESI-MS/MS studies revealed a hitherto unknown contaminant, tris(2-n-butoxyethyl) phosphate (TBEP), which has potential health risks.en
dc.description.affiliationUniv Fed Parana, Dept Bioquim & Biol Mol, BR-81531980 Curitiba, PR, Brazil
dc.description.affiliationIst Ric Chim & Biochim G Ronzoni, I-20133 Milan, Italy
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim & Biol Mol, BR-04044020 São Paulo, SP, Brazil
dc.description.affiliationUniv Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim & Biol Mol, BR-04044020 São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipBrazilian agency Fundacao Araucaria
dc.description.sponsorshipBrazilian agency FINEP (PRONEX-CARBOIDRATOS, PADCT II/SBIO)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent2330-2338
dc.identifierhttp://dx.doi.org/10.1039/c0an01010c
dc.identifier.citationAnalyst. Cambridge: Royal Soc Chemistry, v. 136, n. 11, p. 2330-2338, 2011.
dc.identifier.doi10.1039/c0an01010c
dc.identifier.issn0003-2654
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33299
dc.identifier.wosWOS:000290627500019
dc.language.isoeng
dc.publisherRoyal Soc Chemistry
dc.relation.ispartofAnalyst
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.titleA robust method to quantify low molecular weight contaminants in heparin: detection of tris(2-n-butoxyethyl) phosphateen
dc.typeinfo:eu-repo/semantics/article
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