Comparison of established and novel purity tests for the quality control of heparin by means of a set of 177 heparin samples
| Autor: | Susanne Lühn, Susanne Alban, Knut Baumann, Claudia Schilling, Simone Schiemann, Bernhard Wolf, Magnus Matz, Ulrike Holzgrabe, Tanja Beyer, Oliver Rädler, Jochen Norwig |
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| Rok vydání: | 2010 |
| Předmět: |
Quality Control
Magnetic Resonance Spectroscopy Spectrophotometry Infrared Analytical chemistry Fluorescence spectrometry Dermatan Sulfate Spectrum Analysis Raman Biochemistry Analytical Chemistry Chemometrics medicine Animals Humans Detection limit Chromatography Sheep medicine.diagnostic_test Chromogenic Chemistry Heparin Chondroitin Sulfates Anticoagulants Nuclear magnetic resonance spectroscopy Spectrometry Fluorescence Factor Xa Proton NMR Prothrombin Time Partial Thromboplastin Time Drug Contamination medicine.drug Partial thromboplastin time |
| Zdroj: | Analytical and bioanalytical chemistry. 399(2) |
| ISSN: | 1618-2650 |
| Popis: | The widespread occurrence of heparin contaminated with oversulfated chrondroitin sulfate (OSCS) in 2008 initiated a comprehensive revision process of the Pharmacopoeial heparin monographs and stimulated research in analytical techniques for the quality control of heparin. Here, a set of 177 heparin samples from the market in 2008 as well as pure heparin sodium spiked with defined amounts of OSCS and DS were used to evaluate established and novel methods for the quality control of heparin. Besides 1H nuclear magnetic resonance spectroscopy (NMR), the assessment included two further spectroscopic methods, i.e., attenuated total reflection-infrared spectroscopy (ATR-IR) and Raman spectroscopy, three coagulation assays, i.e., activated partial thromboplastin time (aPTT) performed with both sheep and human plasma and the prothrombin time (PT), and finally two novel purity assays, each consisting of an incubation step with heparinase I followed by either a fluorescence measurement (Inc-PolyH-assay) or by a chromogenic aXa-assay (Inc-aXa-assay). NMR was shown to allow not only sensitive detection, but also quantification of OSCS by using the peak-height method and a response factor determined by calibration. Chemometric evaluation of the NMR, ATR-IR, and Raman spectra by statistical classification techniques turned out to be best with NMR spectra concerning the detection of OSCS. The validity of the aPTT, the current EP assay, could be considerably improved by replacing the sheep plasma by human plasma. In this way, most of the contaminated heparin samples did not meet the novel potency limit of 180 IU/mg. However, also more than 50% of the uncontaminated samples had |
| Databáze: | OpenAIRE |
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