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在生产和贮存低分子量肝素的过程中，糖链上的硫酸酯基团会被水解而损失活性，因此肝素样品中常可以检测到游离的硫酸根离子，此外在生产过程中还会引入其他阴离子。为了检测低分子量肝素的质量稳定性，常用离子色谱检测低分子量肝素中游离的阴离子。但是相对分子质量较大的低分子量肝素会污染离子色谱柱和抑制器。为此发展了一种灵敏的毛细管电泳方法用于测定低分子量肝素中游离的SO2－4、Cl－、F－、PO3－4和OAc－。不同于常用的背景吸收离子铬酸根，采用邻苯二甲酸根作为背景吸收电解质。与铬酸根相比，邻苯二甲酸根与所有待测阴离子电泳淌度匹配得更好，因此可以获得较窄的峰形。而且邻苯二甲酸根在230 nm检测波长下的摩尔吸光系数（4754 L／（mol·cm））比铬酸根（254 nm，2400 L／（mol·cm））高。因此，可以将毛细管电泳检测阴离子的灵敏度提高到与离子色谱法相当的水平。通过验证，该方法在0?002～1 mmol／L的浓度范围内具有较好的线性关系，日内（ n＝6）和日间（ n＝3）迁移时间和峰面积的相对标准偏差均小于3％。所测阴离子的检出限（ S／N＝3）和定量限（ S／N＝10）分别为0?4～0?8μmol／L和2～4μmol／L。该方法可用于监测低分子量肝素的稳定性。

The sulfate ester groups of low molecular weight heparins ( LMWHs) are labile and easily hydrolyzed to produce free sulfate ions during the process of manufacture and storage. In addition, other anions such as chloride and acetylate are often introduced in the products. For monitoring the stability of the products, ion chromatography is the commonly used technique for determining the free anions in LMWHs. However, the column and the suppressor of ion chromatography are easily contaminated by LMWHs due to their relatively large molecules. Therefore, we developed a capillary electrophoresis ( CE ) method with indirect ultraviolet ( UV ) detection for determining the free anions in LMWHs, including sulfate, chloride, fluoride, phosphate and acetate. Unlike the commonly used anion separation CE method which uses chromate as the background absorption electrolyte, phthalate was used as the probe anion because its electrophoretic mobility matches better to all of the anions than chromate so that more narrow peaks could be obtained. Moreover, the molar absorptivity of phthalate at 230 nm ( 4 754 L/( mol·cm) ) was higher than that of chromate at 254 nm ( 2 400 L/( mol·cm) ) . The combination of the narrow peak shape with the high molar absorptivity of the probe ion improves the detection sensitivity nearly to the lever of ion chromatography. Effects of various CE parameters on the separation of the anions were investigated and optimized. The method displayed excellent linearity in the concentration range from 0?002 to 1 mmol/L. The relative standard deviations ( RSDs) for intraday ( n=6) and interday ( n=3) repeatabilities in terms of migration times and peak areas were all less than 3%. The limits of detection ( S/N=3 ) and limits of quantitation ( S/N=10) were determined as 0?4-0?8 μmol/L and 2-4 μmol/L for the above anions, respectively. The method was successfully applied for the stability monitoring of LMWHs.