磷酸盐浓度对测定替卡西林钠/克拉维酸钾(15:1)中高分子杂质分离效果的影响  

The Infl uence of the Separation by Phosphate Buffer for the Determination of High Molecular Mass Impurities in Ticarcillin Disodium and Clavulanate Potassium(15:1)

作　　者：林波[1] 文随方 云冲 向世英 

机构地区：[1]海南医学院海南省肿瘤发生和干预重点实验室,海口571199 [2]海南通用三洋药业有限公司,海口570312

出　　处：《国外医药（抗生素分册）》2015年第1期19-22,共4页World Notes on Antibiotics

基　　金：遵义医学院院基金(F-631;NO.zmk2013-008);贵州省教育厅黔科合人才团队字[2012]03号

摘　　要：目的考察不同浓度的磷酸盐对测定替卡西林钠/克拉维酸钾(15:1)中高分子杂质分离效果的影响,找出较好的磷酸盐缓冲液作为流动相,改进测定替卡西林钠/克拉维酸钾(15:1)中高分子杂质的HPLC分析方法。方法采用高效液相色谱法,以TSK-GELG2500PWxl为色谱柱,检测波长为230nm。以不同浓度的磷酸盐作为流动相,考察替卡西林/钠克拉维酸钾(15:1)中高分子杂质分离效果。结果0.04mol/L磷酸氢二钠-0.04mol/L磷酸二氢钠(95:5)为流动相,流速为0.8mL/min,柱温30℃,高分子杂质与替卡西林及克拉维酸分离效果较好;替卡西林检测限为50ng(S/N≈3),定量限为300ng(S/N≈10);替卡西林在2.154μg/mL^21.538μg/mL浓度范围有良好的线性关系(r=0.99998);高分子杂质在供试品溶液为0.504mg/mL^1.997mg/mL浓度范围内,与峰面积线性关系良好(r=0.9995);重复性较好(RSD=0.50%,n=6)。结论不同浓度的磷酸盐缓冲液对分离效果影响较大,0.04mol/L磷酸氢二钠-0.04mol/L磷酸二氢钠(95:5)为流动相,能较好的检测替卡西林钠克拉维酸钾(15:1)中的高分子杂质。Objective To find a optimum polymer impurity detection method, we investigate the impact of different concentrations of phosphate buffer on HPLC.The method was applied to analyze high molecular mass impurities of sodium ticarcillin/clavulanate potassium injection （15：1）. Methods The HPLC was performed on a TSK-GEL G2500PWxl column.The mobile phase was composed of different concentrations of phosphate buffer; the detection wave length was 230nm. Results The mobile phase consisted of 0.04mol/L disodium hydrogen phosphate solution -0.04 mol/L sodium dihydrogen phosphate solution （95：5） with a flow rate of 0.8 mL/min（the column temperature was 30℃）was better for separation. The detection limit of ticarcillin was 50 ng and the limit of quantitafion was 300 ng.The linearity of ticarcillin solution concentration was between 2.154 gg/mL and 21.538gg/ mL （r=0.99998）; The peak area of high molecular mass impurities showed good linearity in the range of the test solution concentration between 0.504mg/mL and 1.997mg/mL （r=0.9995）. The method showed a good reproducibility and RSD was 1.0% （n=6）. Conclusion Different concentrations of phosphate buffer have a significant effect on the separation method. Phosphate buffer[0.04mol/L disodium hydrogen phosphate solution -0.04 mol/L sodium dihydrogen phosphate solution （95：5）] were better for separation of high molecular mass impurities of the injection.

关 键 词：替卡西林钠 克拉维酸钾 高分子杂质 高效液相色谱法 磷酸盐浓度 分离效果 

分 类 号：R978.11[医药卫生—药品]