柱前衍生化HPLC法测定4-氯-3-(三氟甲基)苯异氰酸酯中CTF-苯胺和CTF-脲  

Determination of CTF-aminobenzene and CTF-urea in 4-chloro-3-(trifluoromethyl) phenyl isocyanate by HPLC after pre-column derivatization

作　　者：赵国敏 郑德强 江玉娟 王秀珍 张利剑 ZHAO Guo-min ZHENG De-qiang JIANG Yu-juan WANG Xiu-zhen ZHANG Li-jian(Key Laboratory for Chemical Drug Research of Shandong Province, Shandong Academy of Pharmaceutical Science, Ji＇ nan 250101 China Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Freda Pharmaceutical Group Co. Ltd, Ji＇ nan 250101, China Shandong Mingren Freda Pharmaceutical Co., Ltd., Ji＇ nan 250104, China)

机构地区：[1]山东省药学科学院,山东省化学药物重点实验室,济南250101 [2]山东福瑞达医药集团公司,山东省黏膜与皮肤给药技术重点实验室,济南250101 [3]山东明仁福瑞达制药股份有限公司,济南250104

出　　处：《药物分析杂志》2016年第12期2226-2230,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：“重大新药创制”科技重大专项(编号:2009ZX09301-013)

摘　　要：目的:建立柱前衍生化HPLC法测定抗癌药物原料4-氯-3-(三氟甲基)苯异氰酸酯中的杂质CTF-苯胺[4-氯-3-(三氟甲基)苯胺]和CTF-脲{1,3-双[4-氯-3-(三氟甲基)苯基]脲}。方法:采用Symmetry C18色谱柱(4.6 mm×150 mm,3.5μm),以0.01 mol·L^(-1)磷酸二氢钾溶液(用2 mol·L^(-1)氢氧化钾溶液调p H至6.5)(A)-乙腈(B)为流动相,梯度洗脱(0~10 min,60%A→40%A;10~20 min,40%A→30%A;20~30 min,30%A→25%A),流速1.0 m L·min^(-1),检测波长260 nm,柱温35℃。结果:CTF-苯胺、CTF-脲质量浓度分别在1.87~46.80和4.15~103.76μg·m L^(-1)范围内呈良好的线性关系,线性关系系数r值均大于0.999 6;平均回收率(n=9)分别为98.7%、98.0%,RSD分别为1.43%、2.36%;定量限分别为0.187μg·m L^(-1)(相当于0.04%)、0.208μg·m L^(-1)(相当于0.04%)。试验测得3批4-氯-3-(三氟甲基)苯异氰酸酯中含CTF-苯胺0.21%、0.22%、0.25%,含CTF-脲1.68%、1.81%、1.24%。结论:经方法学验证,该方法适用于4-氯-3-(三氟甲基)苯异氰酸酯中CTF-苯胺和CTF-脲的测定。Objective： To establish an HPLC method after pre-column derivatization for the determination of CTF-aminobenzene[4-chloro-3-（trifluoromethyl）-benzenamine] and CTF-urea {1, 3-bis （4-chloro-3-（trifluoromethyl）phenyl）urea} in a raw material of anti-cancer drug 4-chloro-3-（trifluoromethyl）phenyl isocyanate.Methods： A Symmetry C18 column （4.6 mm×150 mm, 3.5 μm） was adopted.The mobile phase consisted of 0.01 mol·L-1 KH2PO4 （adjusting pH to 6.5 with 2 mol·L-1 KOH） （A）-acetonitrile （B） with linear gradient elution （0-10 min, 60%A→40%A;10-20 min, 40%A→30%A;20-30 min, 30%A→25%A）.The flow rate was 1.0 mL·min-1 and the detection wavelength was 260 nm.The column temperature was 35℃.Results： CTF-aminobenzene and CTF-urea exhibited good linearity in the ranges of 1.87-46.80 μg·mL-1 and 4.15-103.76 μg·mL-1 （r〉0.999 6） respectively; the average recoveries （n=9） were 98.7% and 98.0%, and RSDs were 1.43% and 2.36%; the limits of quantity were 0.187 μg·mL-1 （equal to 0.04%） and 0.208 μg·mL-1 （equal to 0.04%）.The determination results of three batchs of samples were 0.21%, 0.22%, 0.25% （CTF-aminobenzene） and 1.68%, 1.81%, 1.24% （CTF-urea）, respeclively.Conclusion： The established method is proved to be suitable for the determination of CTF-aminobenzene and CTF-urea in 4-chloro-3-（trifluoromethyl） phenyl isocyanate.

关 键 词：抗癌药物 索拉非尼 瑞戈非尼 4-氯-3-(三氟甲基)苯异氰酸酯 杂质检测 CTF-苯胺 CTF-脲 柱前衍生化 高效液相色谱 

分 类 号：R917[医药卫生—药物分析学]