凝胶色谱法测定比阿培南聚合物含量.docVIP

凝胶色谱法测定比阿培南聚合物含量[摘要] 目的:建立比阿培南聚合物的测定方法。方法:采用葡聚糖凝胶Sephadex G-10不锈钢柱(10 mm×300 mm),流动相A:磷酸盐缓冲液(取磷酸氢二钾5.59 g,与磷酸二氢钾0.41 g,加水使其溶解成1 000 ml);流动相B:水;流速为0.3 ml/min;检测波长为254 nm;进样量为200 μl;柱温为室温;对照品采用法罗培南。结果:比阿培南在100.40～400.55 mg/ml 范围内,浓度与聚合物的峰面积呈良好线性关系(r=0.999 9)。结论:凝胶色谱法方法简便,结果可靠,可以用于比阿培南中高分子聚合物杂质的检测。 [关键词] 凝胶色谱法;比阿培南;聚合物 [中图分类号] R927.2[文献标识码]C [文章编号]1674-4721(2010)03(b)-116-02 Determination of high polyler impurities in Biapenem by gel permeation chromatography MA Jie,ZHAO Yuxin,WANG Guanghui,REN Jiqiu ( Development and Scientific Research Centre,Harbin Pharmaceutical Group CO., LTD. General PharmAceuticalFactory,Heilongjiang Province,Harbin150046, China) [Abstract] Objective:To develop a method for the determination of high polyer impurities in biapenem. Methods:Gel permeation chromatography method was adpoted.The analytical column was Sephadex G-10 stainless steel column (10 mm×300 mm), the mobile phase A:was phosphate buffer(dissolve 5.59 g of potassium dihydrogen phosphate and 0.41 g monopotassium phosphate in water to make 1 000 ml), and the mobile phase B was water; The flow rate was about 0.3 ml per minute; The detective wavelength was 254 nm; The volume of injection was 200 μl; The column temperature was room temperature;Reference standards Faropenem. Results: The calibration curves of high polyler impurities in biapenem was in good linearite over the range of 100.40～400.55 mg/ml(r=0.999 9). Conclusion: Gel permeation chromatography issensitive,specific,accurate and reliable, it is suitable to the determination of high polyler impurities in biapenem. [Key words] Gel permeation chromatography;Biapenem;High polyler 比阿培南是美国Wyeth公司研发的新型1β-甲基碳青霉烯类抗生素。β内酰胺类抗生素变态反应与药物中存在的高分子杂质有关[1-2],β内酰胺类抗生素在以水为流动相中可以缔合形成表观分子量较大的缔合物,缔合物在Sephadex G10凝胶色谱系统中色谱行为和高分子杂质一样,Kav=0处表现为单一色谱峰这一特点,采用了自身对照外标法对高分子杂质进行精确定量[3-4],实验表明比阿培南比较难于在水溶液中聚合,且聚合物分子量与单体相差不大,给分离分析带来难度,但比阿培南在受热时会产生高分子聚合物,因此建议将比阿培南聚合物纳入质量控制指标。本文利用葡聚糖凝胶Sephadex G10色谱系统实现了对比阿培南中高分子聚合物的分离分析。 1 试剂与材料 LC-2