苯溴马隆片含量测定和有关物质检查方法的研究 - 中国药品标准.doc

普卢利沙星片含量和有关物质检测方法的研究 孟长虹, 金卫红, 陆益红 （江苏省食品药品检验所，南京 210008） 摘要 目的：完善普卢利沙星片含量及有关物质的检测方法。方法：采用C18色谱柱，以0.1%磷酸溶液（三乙胺调节pH值至4.0）为流动相A，乙腈为流动相Bg·mL-1浓度范围内，杂质NM394在1.23～39.36g·mL-1浓度范围内呈良好线性关系；含量测定平均回收率为101.3%，RSD为1.46%（n=9）。结论：该法专属性强，灵敏、准确，耐用性好，可作为普卢利沙星片的质量控制方法。 关键词：普卢利沙星片；有关物质；含量测定；高效液相色谱法 中图分类号：R921.2 文献标识码：A 文章编号： Study on Determination and Related Substances of Prulifloxacin Tablets Meng Changhong, Jin Weihong, Lu Yihong (Jiangsu Institute for Food and Drug Control, Nanjing 210008) Abstract Objective：To perfect the HPLC method for determination and related substances of prulifloxacin tablets. Methods：The separation was performed on a C18 column with a mixture of 0.1% phosphoric acid solution (three triethylamine adjusted to pH 4) as mobile phase A，acetonitrile as mobile phase B, isocratic elution A:B (55:45) for determination and gradient elution for related substances. The UV detection wavelength was 278nm. Results：Prulifloxacin was well separated from other impurities. The calibration curve of prulifloxacin was linear in the range of 12.9-413.8g·mL-1 . The calibration curve of impurity NM394 was linear in the range of 1.23-39.36g·mL-1 . The average recoveries (n=9) was 101.3% (RSD=1.46%). Conclusion：The method is proved to be specific, sensitive and accurately and could be used to control the quality of prulifloxacin tablets. Key words：prulifloxacin tablets; related substances;determination; HPLC 普卢利沙星(rulifloxacin)的化学名为(±)6-氟-1-甲基-7-[4-(5-甲基-2-氧代-1,3-二氧杂环戊烯-4-基)-甲基-1-哌啶基]-4-氧代-4H-[1,3] 硫氮杂环丁烷并[3,2-a]喹啉-3-羧酸是由日本Nippon Shinyaku公司研发的氟喹诺酮类抗菌药，于2002年在日本首次上市，商品名Sword。本品是噻丁啶-喹啉羧酸衍生物NM394的脂溶性前体药物它在体内经过双氧酶水解除去C7位上的5-甲基-2-氧-1,3-二氧杂环戊烯，成为NM394(±)-6-氟-1-甲基-7-（1-哌啶基）-4-氧代-4H-[1,3]硫氮丁烷并[3,2-a]喹啉-3-羧酸,NM394通过抑制细菌回旋酶而发挥抗菌活性。NM394 , 特别是对绿脓杆菌为主的革兰阴性菌的抗菌力强, 其不良反应少，耐受性好，作用优于环丙沙星、氧氟沙星和依诺沙星[2]。 双氧酶水解 图1 普卢利沙星降解示意图 经查询国家食品药品监督管理局药品数据库，目前普卢利沙星片生产企业执行的注册标准[3-6] 有多个，均采用高效液相色谱法测定含量和有关物质。通过对这些标准和文献[7-9]中多种测量方法进行比较，发现现行标准在有些条件下主峰和杂质峰分离不理想且有的杂质未能检出。本文在优化色谱条件并综合考虑出峰时间、分离度、理