No abstract

No abstract

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 (1)H and (1)H-(13)C 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.

Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses. Here, to address this issue, NMR spectroscopy and chemometrics were applied to characterize 88 crude heparin samples. The samples were also analyzed by strong anion exchange HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR data differentiated the samples based on their purity. These orthogonal approaches differentiated samples according their glycosaminoglycan (GAG) composition and their mono and disaccharide composition and structure for each GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A). Moreover, quantitative HSQC and multivariate analysis (PCA) were used to distinguish between crude heparin of different animal and tissue sources.

We studied the network structure of elastomers based on polyisoprene, polybutadiene, and their blends in the narrow range of formulations compatible with actual use in the automotive tyre industry. Cross‐link density (CLD) was quantified comparatively by low‐field 1H multiple quantum time domain nuclear magnetic resonance (MQ TD‐NMR) and by equilibrium swelling technique. The robustness and agreement of the two methods was demonstrated in measuring minute alterations of unfilled vulcanizates beyond the optimum cure time. Comparison with samples where polysulfidic bonds were selectively cleaved also demonstrates that the length of the sulfur chain constituting the cross‐link does not significantly affect residual dipolar coupling. Kraus, Lorenz, and Parks correction for filler restriction on swelling is validated by MQ TD‐NMR, which also allows extracting information on cross‐link distribution not provided by swelling measurement. Cross‐link distributions in the blends were demonstrated to be significantly different from the weighted average of the pure samples, while average proton–proton residual dipolar coupling values correspond. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42700.