Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events.
Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.
Guerrini
Marco
M
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Città Studi, via Giuseppe, Colombo 81, 20133 Milan, Italy.
Beccati
Daniela
D
Shriver
Zachary
Z
Naggi
Annamaria
A
Viswanathan
Karthik
K
Bisio
Antonella
A
Capila
Ishan
I
Lansing
Jonathan C
JC
Guglieri
Sara
S
Fraser
Blair
B
Al-Hakim
Ali
A
Gunay
Nur Sibel
NS
Zhang
Zhenqing
Z
Robinson
Luke
L
Buhse
Lucinda
L
Nasr
Moheb
M
Woodcock
Janet
J
Langer
Robert
R
Venkataraman
Ganesh
G
Linhardt
Robert J
RJ
Casu
Benito
B
Torri
Giangiacomo
G
Sasisekharan
Ram
R
D002809:Chondroitin Sulfates / Q000032:analysis* / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006493:Heparin / Q000032:analysis* / Q000737:chemistry*; D006801:Humans
D006493:Heparin; D002809:Chondroitin Sulfates