Analytical and statistical comparability of generic enoxaparins from the US market with the originator product

Abstract

Low-molecular-weight heparins (LMWHs) are complex anticoagulant drugs, made from heparin porcine mucosa starting material. Enoxaparin sodium manufactured by Sanofi is one of the most widely prescribed LMWHs and has been used since 1993 in the USA. In 2010, US Food and Drug Administration approval for supplying generic enoxaparin was granted to Sandoz and subsequently to Amphastar. Little is known, however, of the differences in composition of these preparations. In this study, samples from several batches of generic enoxaparins were purchased on the US market and analyzed with state of the art methodologies, including disaccharide building blocks quantification, nuclear magnetic resonance (NMR), and a combination of orthogonal separation techniques. Direct high-performance liquid chromatography analysis of the different enoxaparin batches revealed distinct process fingerprints associated with each manufacturer. Disaccharide building block analysis showed differences in the degree of sulfation, the presence of glycoserine derivatives, as well as in proportions of disaccharides. Results were compared by statistical approaches using multivariate analysis with a partial least squares discriminant analysis methodology. The variations were statistically significant and allowed a clear distinction to be made between the enoxaparin batches according to their manufacturer. These results were further confirmed by orthogonal analytical techniques, including NMR, which revealed compositional differences of oligosaccharides both in low- and high-affinity antithrombin fractions of enoxaparin.

Contrasting amino acid profiles among permissive and non-permissive hosts of Candidatus Liberibacter asiaticus, putative causal agent of Huanglongbing

“…Using PLS-DA, the most discriminatory FAAs between C Las -permissive hosts and non-permissive plants were identified using the index scores of their variable importance on the projection (VIP) plot. An FAA with a VIP > 1 score is considered important [ 28 ]. The Pearson linear correlation was used to determine relationships between individual FAAs and to identify those FAAs which highly correlated with the host C Las host status.…”

Release Characteristics of Enoxaparin Sodium Loaded Polymethylmethacrylate Bone Cement

“…Polymethylmethacrylate (PMMA) bone cement is extensively used in various medical aspects, including antibiotic loaded carriers, llings for tissue defects, orthopedic implants xation, etc. [1][2][3] . Produced by a beta-elimination lysis of the ordinary heparin sodium, enoxaparin sodium (ES) is the most widely used low molecular weight heparin sodium in the world, with a market share of more than 60% in the United States [4,5] .…”

“…[1][2][3] . Produced by a beta-elimination lysis of the ordinary heparin sodium, enoxaparin sodium (ES) is the most widely used low molecular weight heparin sodium in the world, with a market share of more than 60% in the United States [4,5] . Due to the microporous structure, PMMA bone cement as a drug carrier has been a hot topic in the interdisciplinary research of clinical medication and material sciences [6][7][8] .…”

Heparin Isomeric Oligosaccharide Separation Using Volatile Salt Strong Anion Exchange Chromatography

“…Cetyltrimethylammonium SAX (CTA-SAX) is an alternative SAX method which uses a C8 or C18 column matrix derivatised with CTA [20][21] . The coating of CTA is dynamic and fine tuning of this coat results in the resolution of oligosaccharides containing up to 20 sulfate groups.…”