Differentiation of Generic Enoxaparins Marketed in the United States by Employing NMR and Multivariate Analysis

作者：Guerrini Marco^*; Rudd Timothy R; Mauri Lucio; Macchi Eleonora; Fareed Jawed; Yates Edwin A; Naggi Annamaria; Torri Giangiacomo

来源：Analytical Chemistry, 2015, 87(16): 8275-8283.

DOI：10.1021/acs.analchem.5b01366

The U.S. Food and Drug Administration defines criteria for the equivalence of Enoxaparin with Lovenox, comprising the equivalence of physiochemical properties, heparin source material and mode of depolymerization, disaccharide building blocks, fragment mapping and sequence of oligosaccharide species, biological and biochemical assays, and in vivo pharmacodynamic profile. Chemometric analysis of the NMR spectra, utilizing both H-1 and H-1-C-13 HSQC NMR experiments, of Lovenox and Enoxaparin, the latter being the generic version of the former, revealed that Lovenox and the four Enoxaparin compounds produced by Sandoz (Enoxaparin and Fibrinox), Winthrop, and Amphastar exhibit dissimilarities in terms of their composition. All of the collected samples had expiry dates between 2012 and 2015. These studies, in addition to chromatographic analysis, highlighted signatures that differentiated the branded material from the generic products.

• 出版日期2015-8-18