Please use this identifier to cite or link to this item:
|Title:||A robust method to quantify low molecular weight contaminants in heparin: detection of tris(2-n-butoxyethyl) phosphate|
|Authors:||Sassaki, Guilherme L.|
Riter, Daniel S.
Santana Filho, Arquimedes P.
Lima, Marcelo A. [UNIFESP]
Souza, Lauro M.
Cipriani, Thales R.
Rudd, Timothy R.
Nader, Helena B. [UNIFESP]
Yates, Edwin A.
Gorin, Philip A. J.
Univ Fed Parana
Ist Ric Chim & Biochim G Ronzoni
Universidade Federal de São Paulo (UNIFESP)
|Publisher:||Royal Soc Chemistry|
|Citation:||Analyst. Cambridge: Royal Soc Chemistry, v. 136, n. 11, p. 2330-2338, 2011.|
|Abstract:||Recently, 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.|
|Appears in Collections:||Em verificação - Geral|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.