Chemometric analysis of porcine, bovine and ovine heparins

Ouyang, Yilan; Han, Xianlin; Yu, Yanlei; Chen, Jianle; Fu, Li; Zhang, Fuming; Linhardt, Robert J.; Fareed, Jawed; Hoppensteadt, Debra; Jeske, Walter; Kouta, Ahmed; Zhang, Zhenqing; Xia, Ke

doi:10.1016/j.jpba.2018.10.052

Cited by 17 publications

(13 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is established that bovine heparins exhibit lower anticoagulant activity than porcine heparin (9, 13, 14, 25, 26) Modern analytical techniques have shown this reduced activity of bovine heparin to be associated with differences in the sulfation pattern and presence of antithrombin-binding regions (6, 12, 13, 27, 28). Even with modern refinements to the heparin manufacturing process, the potency of bovine heparins will likely be limited to ~75% that of porcine heparin.…”

Section: Discussionmentioning

confidence: 99%

Bovine Mucosal Heparins Are Comparable to Porcine Mucosal Heparin at USP Potency Adjusted Levels

et al. 2019

Self Cite

View full text Add to dashboard Cite

Introduction: Bovine mucosal heparins (BMH) are currently being developed for re-introduction for both medical and surgical indications. BMH active pharmaceutical ingredient (API) exhibits a somewhat weaker USP potency when compared to PMHs. We hypothesized that when dosages are normalized based on the USP reference heparin, BMH will exhibit comparable in vitro and in vivo effects to those produced by PMH. Therefore, studies were developed to compare the APIs of bovine and porcine heparin.Materials and Methods: API versions of PMH were obtained from Celsus Laboratories (Franklin, OH) and Medefil (Glen Ellen, IL). API versions of BMH were obtained from Kin Master (Passo Fundo, Brazil). Each of these heparins was assayed for their molecular weight profile, AT affinity, USP potency, and anticoagulant/antiprotease profiles using standard laboratory methods. In vitro protamine neutralization studies were carried out. Antithrombotic and hemorrhagic effects were measured in rats and pharmacodynamic profiles were assessed in primates.Results: Size exclusion chromatography demonstrated that the mean molecular weight of BMH was ~15% higher than that of PMH (BMH: 20.1 ± 0.8 kDa and PMH: 17.5 ± 0.7 kDa). BMH exhibited an anti-Xa potency of 130 U/mg while PMH had an anti-Xa potency of 185 U/mg. In the anticoagulant and antiprotease assays, the BMH exhibited lower functionality which was proportional to USP potency. When the BMH was compared with PMH at potency adjusted concentrations, it showed identical concentration-response curves in the aPTT and anti-protease assays. However, in the protamine neutralization studies, BMH required slightly higher amounts of protamine in contrast to PMH. BMH and PMH administered to rats at equivalent anti-Xa unit dosages resulted in comparable antithrombotic activity and prolongation of bleeding time. Similar pharmacodynamic profiles were observed in primates when BMH and PMH were dosed on an anti-Xa U/kg basis.Conclusion: BMH, when used at comparable anti-Xa unit levels, is comparable to PMH, however, it requires proportionally higher amount of protamine due to the increased mass for adjusting to higher potency. Additional studies on the structural characterization, interactions with PF4 and in vivo neutralization studies are ongoing.

show abstract

Section: Discussionmentioning

confidence: 99%

Bovine Mucosal Heparins Are Comparable to Porcine Mucosal Heparin at USP Potency Adjusted Levels

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In heparins' analysis, samples are prepared by dissolving in D 2 O and lyophilizing to remove exchangeable hydrogen from the backbone of the structure. Then, the samples are redissolved in D 2 O to minimize the HDO peak in the NMR spectrum [ 49 , 50 ]. Through one-dimensional (1D) 1 H-NMR spectra and two-dimensional (2D) heteronuclear single quantum coherence spectroscopy- (HSQC-) NMR, St Ange et al [ 50 ] verified the structural similarities and differences between bovine and porcine heparins.…”

Section: Analysis Of Heparinsmentioning

confidence: 99%

“…Liquid Chromatography- (LS-) MS. LS-MS is a combination of LS and MS, LS can effectively separate the organic compounds in the samples, and MS is able to analyze the separated organic compounds in order to obtain the information on their molecular weight, structures, and concentrations. It is worth noting that, before the LS-MS heparin analysis, the samples need to be boiled and centrifuged to remove the heparinase; then the supernatants required to be lyophilized and redissolved [ 49 , 53 ]. Ouyang et al [ 48 ] developed LC-MC analysis method which can detect adulterant of 10% bovine or ovine heparin in porcine heparin.…”

Section: Analysis Of Heparinsmentioning

confidence: 99%

“…Combined techniques CE-MS has shown high efficiency and sensitivity for the analysis of heparin oligosaccharides and LMWH [ 61 , 62 ]. Ouyang et al [ 49 ] developed a CE-MS method, in which the jobs involved with the removal of sulfonic group and the selective chemical derivation of oligosaccharides are not required, compared to LS-MS. Furthermore, the oligosaccharides of heparin have a large negative charge, which are ideal preconditions for tandem mass spectrometry analysis [ 51 ].…”

Section: Analysis Of Heparinsmentioning

confidence: 99%

See 1 more Smart Citation

Techniques for Detection of Clinical Used Heparins

Zhao

2021

International Journal of Analytical Chemistry

View full text Add to dashboard Cite

Heparins and sulfated polysaccharides have been recognized as effective clinical anticoagulants for several decades. Heparins exhibit heterogeneity depending on the sources. Meanwhile, the adverse effect in the clinical uses and the adulteration of oversulfated chondroitin sulfate (OSCS) in heparins develop additional attention to analyze the purity of heparins. This review starts with the description of the classification, anticoagulant mechanism, clinical application of heparins and focuses on the existing methods of heparin analysis and detection including traditional detection methods, as well as new methods using fluorescence or gold nanomaterials as probes. The in-depth understanding of these techniques for the analysis of heparins will lay a foundation for the further development of novel methods for the detection of heparins.

show abstract

“…Bovine, ovine, and porcine heparin samples were completely separated using both PCA and K-means. It suggested that 1 H-NMR spectroscopy, in combination with chemometrics, offers a powerful technique for the authentication of pharmaceutical products such as heparin [ 82 ].…”

Section: Application Of Molecular Spectroscopy Combined With Chemomentioning

confidence: 99%

The Application of Molecular Spectroscopy in Combination with Chemometrics for Halal Authentication Analysis: A Review

Rohman

Windarsih

2020

IJMS

View full text Add to dashboard Cite

Halal is an Arabic term used to describe any components allowed to be used in any products by Muslim communities. Halal food and halal pharmaceuticals are any food and pharmaceuticals which are safe and allowed to be consumed according to Islamic law (Shariah). Currently, in line with halal awareness, some Muslim countries such as Indonesia, Malaysia, and Middle East regions have developed some standards and regulations on halal products and halal certification. Among non-halal components, the presence of pig derivatives (lard, pork, and porcine gelatin) along with other non-halal meats (rat meat, wild boar meat, and dog meat) is typically found in food and pharmaceutical products. This review updates the recent application of molecular spectroscopy, including ultraviolet-visible, infrared, Raman, and nuclear magnetic resonance (NMR) spectroscopies, in combination with chemometrics of multivariate analysis, for analysis of non-halal components in food and pharmaceutical products. The combination of molecular spectroscopic-based techniques and chemometrics offers fast and reliable methods for screening the presence of non-halal components of pig derivatives and non-halal meats in food and pharmaceutical products.

show abstract

Chemometric analysis of porcine, bovine and ovine heparins

Cited by 17 publications

References 21 publications

Bovine Mucosal Heparins Are Comparable to Porcine Mucosal Heparin at USP Potency Adjusted Levels

Bovine Mucosal Heparins Are Comparable to Porcine Mucosal Heparin at USP Potency Adjusted Levels

Techniques for Detection of Clinical Used Heparins

The Application of Molecular Spectroscopy in Combination with Chemometrics for Halal Authentication Analysis: A Review

Contact Info

Product

Resources

About