论文部分内容阅读
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 a pre-column derivatization HPLC method for the determination of CTF-aniline [4-chloro-3- (trifluoromethyl) aniline] in the anticancer drug 4-chloro-3- Urea {1,3-bis [4-chloro-3- (trifluoromethyl) phenyl] urea}. Methods: Symmetry C18 column (4.6 mm × 150 mm, 3.5 μm) was used to adjust the concentration of potassium molybdate in 0.01 mol·L -1 potassium dihydrogen phosphate solution (with 2 mol·L -1 potassium hydroxide solution) (0 to 10 min, 60% A → 40% A; 10 to 20 min, 40% A → 30% A; 20 to 30 min , 30% A → 25% A, flow rate 1.0 m L · min -1, detection wavelength 260 nm, column temperature 35 ℃. Results: The linear ranges of CTF-aniline and CTF-urea in the range of 1.87 ~ 46.80 and 4.15 ~ 103.76μg · m L ~ (-1) were linear and the linear correlation coefficients (r) were all greater than 0.999 6. The average recoveries (n = 9) were 98.7% and 98.0%, respectively, with RSDs of 1.43% and 2.36%, respectively. The limits of quantification were 0.187μg · m L -1 (equivalent to 0.04%), 0.208μg · m L ~ -1) (equivalent to 0.04%). Three lots of CTF-aniline 0.21%, 0.22%, 0.25% and CTF-urea 1.68%, 1.81%, 1.24% were tested in 3 lots of 4-chloro-3- (trifluoromethyl) benzene isocyanate. CONCLUSION: This method is validated by method validation for the determination of CTF-aniline and CTF-urea in 4-chloro-3- (trifluoromethyl) benzene isocyanate.