HPLC法测定枸橡酸托法替布中残留溶剂甲酸和氰乙酸含量  

Determination of residual solvent formic acid and cyanoacetic acid in tofacitinib citrate by HPLC

作　　者：石丽娟 程贯军 王莉 许敏 李慧 吴诺 耿燕楠[2] 江玉娟 SHI Li-juan;CHENG Guan-jun;WANG Li;XU Min;LI Hui;WU Nuo;GENG Yan-nan;JIANG Yu-juan(Shandong Mingren Freda Pharm.Co.,Ltd.,Jinan 250104,China;Department of Pharmacy,Afiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Kongjiang Senior High School,Shanghai 200093,China)

机构地区：[1]山东明仁福瑞达制药股份有限公司,济南250104 [2]山东中医药大学附属医院药学部,济南250014 [3]上海市控江中学,上海200093

出　　处：《药物分析杂志》2025年第2期290-296,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立HPLC法测定枸橡酸托法替布中残留溶剂甲酸和氰乙酸的含量。方法:采用Waters AtlantisT3(250mm×4.6mm,5μm)色谱柱,以0.02mol·L^(-1)磷酸二氢钾溶液(用磷酸调pH2.5)-甲醇为流动相,梯度洗脱,流速0.5mL·min^(-),柱温35℃,检测波长210 nm。结果:甲酸、氰乙酸与相邻峰分离度良好(R≥5);分别在9.930~107.780μg·mL^(-1)、14.727~98.908μg·mL^(-1)浓度内线性关系良好(r=0.9999、0.9998);平均回收率(n=9)分别为100.2%、105.3%,RSD分别为2.3%、4.1%。稳定性考察(18个月)3批枸橡酸托法替布中含氰乙酸0.024%、0.026%、0.028%。结论:经方法学验证,本法可用于枸橡酸托法替布中甲酸和氰乙酸的含量测定。Objective:To establish an HPLC method for the determination of residual solvent formic acid and cyanoacetic acid content in tofacitinib citrate.Methods:The separation was performed on a Waters Atlantis T3(250 mm×4.6 mm,5μm)column with a gradient elution of 0.02 mol·L^(-1)potassium dihydrogen phosphate(pH was adjusted to 2.5 with phosphoric acid)(A)-methanol(B)as the mobile phases.The flow rate was 0.5 mL·min^(-1)and the column temperature was 35 C.Detection wavelength was 210 nm.Results:Formic acid and cyanoacetic acid were well separated from the adjacent peaks(R>5).The linearity was good in the concentration ranges of 9.930-107.780μg·mL^(-1)and 14.727-98.908μg mL^(-1)(r=0.9999,0.9998),respectively.The average recoveries(n=9)were 100.2%and 105.3%,with RSDs of 2.3%and 4.1%,respectively.The determination results of three batches of samples were 0.024%,0.026%,0.028%(cyanoacetic acid),respectively.Conclusion:The established method is proved to be suitable for the determination of formic acid and cyanoacetic acid in tofacitinib citrate.

关 键 词：枸橡酸托法替布 溶剂残留 甲酸 氰乙酸 含量测定 方法学验证 高效液相色谱 

分 类 号：R917[医药卫生—药物分析学]