RP-HPLC手性流动相添加剂法拆分甲磺酸帕珠沙星对映体的研究  

Study on the enantiomer separation of pazufloxacin mesylate by RP-HPLC using chiral mobile phase additives

作　　者：张哲峰[1] 杨更亮[1] 梁贵键[2] 陈义[3] 

机构地区：[1]河北大学化学与环境学院 [2]空军总医院,北京100850 [3]中国科学院化学所分子科学中心,北京100080

出　　处：《中国抗生素杂志》2004年第1期19-22,共4页Chinese Journal of Antibiotics

基　　金：国家自然科学基金资助项目(20375010);河北省基金资助项目(202096;0224501-D);科技部资助(2002CCA3100;KJCX2-H4);教育部优秀青年教师资助

摘　　要：目的建立新药甲磺酸帕珠沙星(PZLX)对映体手性流动相HPLC拆分方法。方法通过探讨流动相pH值、有机改性剂、手性配合剂、反相固定相对手性拆分的影响,确定甲醇-苯丙氨酸溶液(L-苯丙氨酸1.32g与硫酸铜1g,加水1000ml,氢氧化钠试液调节pH值为3.5)(30∶70)为手性流动相,在ODS柱上拆分PZLX对映体,332nm波长检测。结果两对映体良好分离,分离度1.9以上,S、R异构体回归方程分别为:Y=1.38×105X-130.9(r=0.9998)和Y=1.26×105X-60.6(r=0.9998),最低检出限分别为1.2和1.5ng,RSD为0.2%以下。结论所建立的方法简便易行,克服了该类方法灵敏度及重现性不如手性固定相法(CSP)的不足,可用于新药PZLX光学纯度的质量控制及其生物体内代谢立体选择性的研究。Objective To establish an HPLC method for separating and determining the enantiomers of pazufloxacin mesylate.Methods By optimizing factors which affect the chiral separation,the pH value of the mobile phase, the organic modifiers,chiral additives,and stationary phases,the optimum condition for chiral separation were selected.The enantiomers separation was carried out on Shimandzu ODS column(150mm×6.3mm,10μm),and methanol-phenylalanine solution(containing 8mmol/L L-phenylalanine and 6.3 mmol/L copper sulphate,adjusted to pH=3.5 with sodium hydroxide solution)(30∶70) as the chiral mobile phase,detecting on wavelength at 332nm. Results The two enantiomers could be baseline separated,and the resolution was higher than 1.9.Calibration graphs were constructed in the range of 25～250μg/ml for S-(-)-and R-(+)-enantiomer,respectively.The linear regression equations are:Y=1.38×105X-130.9 (r=0.9998)and Y=1.26×105X-60.6 (r=0.9998),respectively.The detection limits obtained by S/N=3 were 1.2ng for S-(-)-and 1.5ng for R-(+)-enantiomer,respectively.Conclusions The proposed method was simple,sensitive,accurate and reproducible,and it can be used for the quality control of the pazufloxacin mesylate enantiomers.

关 键 词：甲磺酸帕珠沙星 对映体 手性分离: 高效液相色谱 手性流动相添加剂法 

分 类 号：R917[医药卫生—药物分析学]