依诺肝素钠宽分布相对分子质量对照品研制

Preparation of A Relative Molecular Mass Reference Substance with Broad Distribution for Enoxaparin Sodium

目的研制一种依诺肝素钠宽分布相对分子质量(Mr)对照品。方法以肝素钠为起始原料,经过成盐、酯化、β-消除降解等步骤制备依诺肝素钠宽分布Mr对照品;以欧洲药典低分子肝素(LMWH)Mr对照品为对照,利用高效分子排阻色谱法(HPSEC)测定自制依诺肝素钠宽分布Mr对照品的Mr及其分布,并与EP对照品比较。分别用自制对照品与EP对照品检测依诺肝素钠原料药的Mr及其分布,并比较检测结果。结果自制对照品与EP对照品的UV图谱与RI图谱相近,Mr及其分布接近,两种对照品测得依诺肝素钠Mr及其分布接近。结论以β-消除降解法制备的依诺肝素钠宽分布Mr对照品可准确测定依诺肝素钠的Mr及其分布,为不同LMWH按各自生产工艺制备其Mr对照品提供参考。

Objective To establish a relative molecular mass （Mr） reference substance （RS） with broad distribution for enoxaparin sodium. Methods A Mr RS with broad distribution for enoxaparin sodium was produced through a series of steps including salification, esterification and β-elimination degradation, using heparin sodium as starting material. Using EP chemical reference substance （CRS） for LMWH as reference substance, the Mr and its distribution of the self-prepared RS with broad distribution was tested by high performance size exclusion chromatography （HPSEC）, and compared with Mr and its distribution of EP Mr CRS. The Mr and Mr distribution of several lots of enoxaparin sodium were tested using self-made RS and EP CRS, and the results were compared. Results The UV and RI chromatograms and the Mr and Mr distribution of the self-made RS and EP CRS were similar. The Mr results of enoxaparin sodium were also of no significant difference. Conclusion The enoxaparin sodium Mr RS prepared through β-elimination degradation can accurately test the Mr and Mr distribution of enoxaparin sodium, which providing a reference for preparation of different LMWH Mr RS.