反相高效液相色谱法同时测定丁酸氯维地平中10种相关杂质  

Development and Validation of a High Performance Liquid Chromatographic Method for Simultaneous Determination of Ten Process-related Impurities of Clevidipine Butyrate

作　　者：刘艳华[1] 吕狄亚[2] 宋志勇[3] 郑滨兴 张倩倩[1,2] 陆峰[2] 许激扬[1] 

机构地区：[1]中国药科大学生命科学与技术学院,南京210009 [2]第二军医大学药学院,上海200082 [3]太原理工大学化学化工学院,太原030024

出　　处：《分析化学》2015年第2期257-263,共7页Chinese Journal of Analytical Chemistry

基　　金："重大新药创新"科技重大专项资助项目(No.2012ZX09202101-001)

摘　　要：建立反相高效液相色谱辅-光电二极管阵列检测器（ RP-HPLC）法同时测定丁酸氯维地平原料药中的10种杂质。色谱柱为 Symmetry C18柱（250 mm×4.6 mm,5μm）,流动相为0.05 mol/L NaH2PO4溶液（pH 2.5）-乙腈/甲醇（3：2, V/V）,梯度洗脱,柱温35℃,流速为1.5 mL/min,检测波长220 nm。丁酸氯维地平及其10个已知杂质能够达到良好的分离,且各组分在各自测定浓度范围内与峰面积的线性关系良好（r≥0.9970）；丁酸氯维地平及杂质1~10的检出限（S/N=3）在0.15~0.90 mg/L之间。本方法快速、简便、有效,可用于丁酸氯维地平原料药的质量控制管理。A reversed phase high performance liquid chromatographic （ RP-HPLC） method coupled with DAD was developed for the simultaneous determination of ten process-related impurities （ PRI ） of Clevidipin Butyrate （ CLE）. The chromatographic separation was carried out on a Waters symmetry C18 column （250 mm ×4. 6 mm, 5 μm） and all components were monitored at 220 nm. The mobile phase consisted of 0. 05 mol/L sodium dihydrogen phosphate with pH 2. 5 adjusted by phosphoric acid （ MPA ） and a mixed solution of acetonitrile and methanol （3：2, V/V）. Flow rate was kept at 1. 5 mL/min, the injection volume was 20 μL for all injections, and the column temperature maintained at 35 ℃. The method was further validated with respect to selectivity, linearity, limit of detection （ LOD ）, limit of quantitation （ LOQ ）, precision and accuracy. A good linearity was obtained in the measured concentration ranges for CLE and ten impurities （ r≥0. 9970 ）, and the detection limits were 0. 90, 0. 24, 0. 23, 0. 15, 0. 18, 0. 18, 0. 27, 0. 82, 0. 45, 0. 89 and 0. 45 mg/L for CLE and ten impurities respectively.

关 键 词：丁酸氯维地平 高效液相色谱 质量控制 

分 类 号：TQ460.72[医药卫生—药物分析学] O657.72[化学工程—制药化工]