氨甲苯酸原料药有机杂质分析方法研究

Development of Analysis Method for Organic Impurities in Aminomethylbenzoic Acid

研究建立氨甲苯酸原料药有机杂质的检测方法。采用高效液相色谱法,C18色谱柱,流动相以0.23%十二烷基硫酸钠溶液(取磷酸二氢钠0.1 mol,加水800 mL溶解,加三乙胺8.3 mL混匀后,再加入十二烷基硫酸钠2.3 g,振摇使溶解,用磷酸调节p H=2.5,加水至1000 mL,摇匀)-甲醇(70∶30)为流动相,流速1.0 mL·min,检测波长230 nm,柱温30℃。结果表明:在选用的条件下,对氨基苯甲酸、3-(氨甲基)苯甲酸、对甲基苯甲酸、2-(氨甲基)苯甲酸4种杂质分别在浓度范围0.02~0.56μg·mL^(-1)(r=0.9999)、0.02~0.49μg·mL^(-1)(r=0.9999)、0.02~0.46μg·mL^(-1)(r=0.9999)、0.02~0.51μg·mL^(-1)(r=0.9999)之间线性关系良好,各杂质平均回收率在92%~103%之间。本方法专属性好、灵敏度高、回收良好,可以很好的控制氨甲苯酸原料药的有机杂质。

A method for the detection of organic impurities in aminomethylbenzoic acid was established.High performance liquid chromatography,C18 column,The mobile phase was 0.23%sodium dodecyl sulfate solution(take 0.1 mol sodium dihydrogen phosphate,add 800 mL water to dissolve,add 8.3 mL triethylamine to mix,then add 2.3 g sodium dodecyl sulfate,shake to dissolve,adjust pH=2.5 with phosphoric acid,add water to 1000 mL,shake well)-methanol(70∶30)as the mobile phase at the flow rate 1.0 mL·min,detection wavelength 230 nm,column temperature 30℃.The results show that under the selected conditions,the four impurities of p-aminobenzoic acid,3-(aminomethyl)benzoic acid,p-toluic acid and 2-(aminomethyl)benzoic acid are in the concentration range of 0.02~0.56μg·mL^(-1)(r=0.9999),0.02~0.49μg·mL^(-1)(r=0.9999),0.02~0.46μg·mL^(-1)(r=0.9999),0.02~0.51μg·mL^(-1)(r=0.9999)had good linear relationships,and the average recoveries of each impurity were between 92%~103%.The method has good specificity,high sensitivity and good recovery,and good control organic impurities of aminomethylbenzoic acid.