Monitoring the purity of pharmaceutical heparin preparations by high-field 1H-nuclear magnetic resonance spectroscopy.
High-field (300 MHz) 1H NMR spectral analyses are reported for various sodium or calcium heparin products available on the Canadian market. Dermatan sulfate (chondroitin sulfate B) was detected as a contaminant in virtually all of these products. Its content varied among the suppliers from less than 1 to 15%, and also over nearly the same range within the groups of heparin preparations of particular suppliers. No correlation was found between in vitro biological activities (potency and anti-factor Xa by the USP tests) and the levels of dermatan sulfate found. Other components, or unlisted constituents, detected in some preparations were paramagnetic metal ions, polyols, and lidocaine.
Neville
G A
GA
Bureau of Drug Research, Health and Welfare Canada, Ottawa, ON.
Mori
F
F
Holme
K R
KR
Perlin
A S
AS
D055598:Chemical Phenomena; D002621:Chemistry; D003871:Dermatan Sulfate / Q000032:analysis; D004492:Edetic Acid / Q000032:analysis; D015951:Factor Xa; D006493:Heparin / Q000302:isolation & purification* / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000032:analysis / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D015842:Serine Proteinase Inhibitors
D006495:Heparin, Low-Molecular-Weight; D015842:Serine Proteinase Inhibitors; D003871:Dermatan Sulfate; D006493:Heparin; D004492:Edetic Acid; D015951:Factor Xa