Quantification of chondroitin sulfate and dermatan sulfate in danaparoid sodium by (1)H NMR spectroscopy and PLS regression.
Summary of "Quantification of chondroitin sulfate and dermatan sulfate in danaparoid sodium by (1)H NMR spectroscopy and PLS regression."
Danaparoid sodium (the active pharmaceutical ingredient in Orgaran; Merck Sharp and Dohme) is a biopolymeric non-heparin drug used as anticoagulant and antithrombotic agent approved for the prophylaxis of post-operative deep-vein thrombosis, which may lead to pulmonary embolism in patients undergoing, e.g., elective hip replacement surgery. It consists of a mixture of three glycosaminoglycans (GAGs): heparan sulfate (HS), dermatan sulfate (DS), and chondroitin sulfate (CS). Currently, the CS and DS content are quantified by means of a time-consuming enzymatic method. In this paper the use of (1)H NMR in combination with multivariate regression (partial least-squares, PLS) is proposed as a new method. In order to evaluate the proposed method, a series of danaparoid sodium samples were analyzed and the results were compared with those obtained by the enzymatic method (reference method). The results showed that the proposed (1)H NMR method is a good alternative for analysis of CS and DS in danaparoid sodium. Accuracy of ±0.7% (w/w) and ±1.1% (w/w) for CS and DS was obtained by the (1)H NMR method and accuracy of ±1.0% (w/w) and ±1.3% (w/w) by the enzymatic method. Furthermore, the use of (1)H NMR in combination with PLS results in a fast quantification. The analysis time is reduced to 35 min per sample instead of 60 h for a maximum of 16 samples.
Affiliation
Merck Sharp and Dohme, Quality Unit API/Biotech NL, Analytical Science Chemicals, P.O. Box 20, 5340 BH, Oss, The Netherlands, bulent.ustun@merck.com.
Journal Details
This article was published in the following journal.
Name: Analytical and bioanalytical chemistry
ISSN: 1618-2650
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20862579
- DOI: http://dx.doi.org/10.1007/s00216-010-4193-7
Medical and Biotech [MESH] Definitions
Chondroitin Sulfates
Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.
Chondroitin Lyases
Enzymes which catalyze the elimination of delta-4,5-D-glucuronate residues from polysaccharides containing 1,4-beta-hexosaminyl and 1,3-beta-D-glucuronosyl or 1,3-alpha-L-iduronosyl linkages thereby bringing about depolymerization. EC 4.2.2.4 acts on chondroitin sulfate A and C as well as on dermatan sulfate and slowly on hyaluronate. EC 4.2.2.5 acts on chondroitin sulfate A and C.
N-acetylgalactosamine-4-sulfatase
An arylsulfatase that catalyzes the hydrolysis of the 4-sulfate groups of the N-acetyl-D-galactosamine 4-sulfate units of chondroitin sulfate and dermatan sulfate. A deficiency of this enzyme is responsible for the inherited lysosomal disease, Maroteaux-Lamy syndrome (MUCOPOLYSACCHARIDOSIS VI). EC 3.1.6.12.
Dermatan Sulfate
A naturally occurring glycosaminoglycan found mostly in the skin and in connective tissue. It differs from CHONDROITIN SULFATE A (see CHONDROITIN SULFATES) by containing IDURONIC ACID in place of glucuronic acid, its epimer, at carbon atom 5. (from Merck, 12th ed)
Chondroitinases And Chondroitin Lyases
Enzymes which catalyze the elimination of glucuronate residues from chondroitin A,B, and C or which catalyze the hydrolysis of sulfate groups of the 2-acetamido-2-deoxy-D-galactose 6-sulfate units of chondroitin sulfate. EC 4.2.2.-.
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