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, 5 μm) 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 ℃. 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 9.930-107.780 μg · mL-1 and 14.727-98.908 μg · mL-1 (r = 0.999 9, 0.999 8), 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.
SHI Li-juan
,
CHENG Guan-jun
,
WANG Li
,
XU Min
,
LI Hui
,
WU Nuo
,
GENG Yan-nan
,
JIANG Yu-juan
. Determination of residual solvent formic acid and cyanoacetic acid in tofacitinib citrate by HPLC[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(2)
: 290
-296
.
DOI: 10.16155/j.0254-1793.2024-0422
[1] 张霞,李宏,张华铃,等.正相高效液相色谱法测定枸橼酸托法替尼原料及片剂中对映异构体[J].药物分析杂志,2017,37(7):1291
ZHANG X,LI H,ZHANG HL,et al.Determination of enantiomer in tofacitinib citrate bulk drug and tablets by normal-phase HPLC[J].Chin J Pharm Anal,2017,37(7):1291
[2] 刘永波. HPLC法测定枸橼酸托法替布片的含量[J].广东化工,2022,49(6):192
LIU YB.Content determination of active ingredients in tofacitinib citrate tablets by HPLC[J].Guangdong Chem Ind J,2022,49(6):192
[3] 张婷,郭颖昕,陈伟燕,等.反相高效液相色谱测定枸橼酸托法替布有关物质的方法学研究[J].上海化工,2021,46(1):33
ZHANG T,GUO YX,CHEN WY,et al.Methodological study on the determination of related substances of tofacitinib citrate by reversed-phase high performance liquid chromatography[J].Shanghai Chem Ind J,2021,46(1):33
[4] 吕佳徽. 枸橼酸托法替尼的工艺优化及质量研究[D].济南:山东大学,2019
LYU JH.Synthesis Process Optimization and Quality Research of Tofacitinib Citrate [D].Jinan:Shandong University,2019
[5] ICH.Q3A(R2)Impurities in New Drug Substances [EB/OL].(2006-10-25) [2024-04-28].https://database.ich.org/sites/default/files/Q3A%28R2%29%20Guideline.pdf
[6] ICH.Q3C(R8)Residual Solvents Guideline [EB/OL].(2020-03-25) [2024-04-28].https://database.ich.org/sites/default/files/ICH_Q3C%28R9%29_Guideline_MinorRevision_2024_2024_Approved.pdf
[7] 中华人民共和国药典2020年版.四部[S].2020:116
ChP 2020.Vol Ⅳ[S].2020:116
[8] 钟宝欣,向以东,宋世丘.气相法测定头孢他啶原料药中甲酸残留的含量[J].今日药学,2016,26(7):489
ZHONG BX,XIANG YD,SONG SQ.Determination of residual formic acid in ceftazidime pentahydrate bulk drug by gas chromatography[J].Pharm Today,2016,26(7):489
[9] 李超. 顶空毛细管气相色谱法测定克林霉素磷酸酯中甲酸残留量[J].中国药业,2017,26(14):14
LI C.Determination of formic acid residue in clindamycin phosphate by headspace capillary gas chromatography[J].China Pharm,2017,26(14):14
[10] 马建兵,郑学明,尚会建,等.氰乙酸的研究及应用[J].河北工业科技,2009,26(5):393
MA JB,ZHENG XM,SHANG HJ,et al.Research and application of cyanoacetic acid[J].Hebei J Ind Sci Technol,2009,26(5):393
[11] 郑滔,陈鹏,汪华,等.气相色谱法测定盐酸羟胺中甲酸[J].云南化工,2023,50(4):61
ZHENG T,CHEN P,WANG H,et al.Determination of formic acid in hydroxylamine hydrochloride by gas chromatograph[J].Yunnan Chem Ind J,2023,50(4):61
[12] 姜艳玲,赵敏,李小宁,等.柱前衍生-气相色谱法测定非布司他残留溶剂甲酸的含量[J].浙江化工,2023,54(6):50
JIANG YL,ZHAO M,LI XN,et al.Determination of residual solvent formic acid content in febuxostat by gas chromatography with pre-column derivatization[J].Zhejiang Chem Ind J,2023,54(6):50
[13] 熊晓毅,陈安群,何咏梅.高效液相色谱测定氰乙酸的含量[J].广州化工,2010,38(12):197
XIONG XY,CHEN AQ,HE YM.Analysis of cyanoacetic acid content by HPLC[J].Guangzhou Chem Ind J,2010,38(12):197
[14] 陈宇. 反相高效液相色谱法测定达托霉素溶液中残留溶剂甲酸、乙酸[J].饮食保健,2017,4(16):301
CHEN Y.Determination of residual solvents formic acid and acetic acid in daptomycin solution by reversed-phase HPLC[J].Diet Health,2017,4(16):301
[15] 辛梅华,李明春,徐金瑞,等.反相高效液相色谱法测定酸雨中的甲酸、乙酸、丙酸等[J].环境工程,2003,21(1):57
XIN MH,LI MC,XU JR,et al.Determination of formic acid,acetic acid and propionic acid in acid rain by reversed-phase HPLC[J].Environ Eng,2003,21(1):57
[16] 许娟,方芳,陈云建,等.高效液相色谱法测定卡络磺钠中甲酸的残留量[J].分析试验室,2017,36(5):609
XU J,FANG F,CHEN YJ,et al.Determination of formic acid residue in sodium carboxysulfonate by high performance liquid chromatography[J].Anal Lab,2017,36(5):609
