Stable Isotopic Analysis of Porcine, Bovine, and Ovine Heparins

作者：Jasper John P^*; Zhang Fuming; Poe Russell B; Linhardt Robert J

来源：Journal of Pharmaceutical Sciences, 2015, 104(2): 457-463.

DOI：10.1002/jps.24134

• heparin
• stable isotopic analysis
• animal sourced
• principle component analysis
• mass spectrometry
• analysis

The assessment of provenance of heparin is becoming a major concern for the pharmaceutical industry and its regulatory bodies. Batch-specific [carbon (C-13), nitrogen (N-15), oxygen (O-18), sulfur (S-34), and hydrogen (D)] stable isotopic compositions of five different animal-derived heparins were performed. Measurements readily allowed their differentiation into groups and/or subgroups based on their isotopic provenance. Principle component analysis showed that a bivariate plot of C-13 and O-18 is the best single, bivariate plot that results in the maximum discrimination ability when only two stable isotopes are used to describe the variation in the data set. Stable isotopic analyses revealed that (1) stable isotope measurements on these highly sulfated polysaccharide (molecular weight approximate to 15 kDa) natural products (biologics) were feasible; (2) in bivariate plots, the C-13 versus O-18 plot reveals a well-defined relationship for source differentiation of hogs raised in the United States from hogs raised in Europe and China; (3) the D versus O-18 plot revealed the most well-defined relationship for source differentiation based on the hydrologic environmental isotopes of water (D/H and O-18/O-16); and (4) the N-15 versus O-18 and S-34 versus O-18 relationships are both very similar, possibly reflecting the food sources used by the different heparin producers.

• 出版日期2015-2