Prediction of the oversulphated chondroitin sulphate contamination of unfractionated heparin by ATR-IR spectrophotometry.
The detection of a contamination of heparin with oversulphated chondroitin sulphate (OSCS) was first analysed in an unfractionated heparin batch supplied to the US API-market in April 2006. OSCS is a semi-synthetic derivative of the natural occuring glycosaminoglycan chondroitin sulphate. Moreover some spectroscopic characteristics of the substance overlap with those of heparin, so that the infrared (IR) spectra are visually difficult to distinguish whereas (1)H-NMR (Nuclear Magnetic Resonance) spectroscopy or capillary electrophoresis (CE) provides identification by a simple visual inspection of either the spectrum or the electropherogram respectively. However, applying special tools of Multivariate Data Analysis (MVA) to the IR spectra an identification of the contaminated samples is possible. In detail a rapid Attenuation Total Reflectance-Infrared (ATR-IR) measurement was selected, which does not require any sample preparation. The result (contaminated or not contaminated) is predicted within a few minutes. A method transfer to mobile ATR-IR spectrometers seems to be possible. The analysis is based on the fact that the fingerprint of the OSCS IR spectrum (1st derivative) complies with a theoretically calculated principal component in the MVA.
Norwig
J
J
Federal Institute for Drugs and Medical Device (BfArM), PAT Group of the Federal Institute, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany. j.norwig@bfarm.de
Beyer
T
T
Brinz
D
D
Holzgrabe
U
U
Diller
M
M
Manns
D
D
D000704:Analysis of Variance; D002138:Calibration; D002809:Chondroitin Sulfates / Q000032:analysis*; D003871:Dermatan Sulfate / Q000032:analysis; D004340:Drug Contamination; D006493:Heparin / Q000032:analysis*; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy; D015233:Models, Statistical; D025341:Principal Component Analysis; D013055:Spectrophotometry, Infrared; D013431:Sulfates / Q000032:analysis*
D013431:Sulfates; D003871:Dermatan Sulfate; D006493:Heparin; D002809:Chondroitin Sulfates