Objective: To establish a method for determination genotoxic impurity furfural in furosemide and its tablets. To analyze and evaluate the measurement results to provide a reference for national drug supervision and ensure drug safety. Methods: The chromatographic column was filled with octadecylsilane bonded silica gel, and the gradient elution was performed with phosphoric acid solution and acetonitrile as the mobile phase. The detection wavelength was 276 nm. The method was validated and used to determine the furfural content in 6 batches of furosemide and 148 batches of furosemide tablets. Results: The detection limit of furfural was 4 ng·mL-1 and the quantitation limit was 12 ng·mL-1. The linearity between 0.012 0-0.602 3 μg·mL-1 (r=1.000) was good. The average recoveries of furosemide and its tablets were 99.4% (RSD=0.99%) and 101.4% (RSD=1.3%). Furfural was detected in all batches of raw materials and tablet samples. The furfural content in the tablet products, which used the raw materials from company I, was significantly higher than that of the products obtained from company H. Conclusion: This method has strong specificity, high sensitivity and good accuracy. It can be used for the determination of genotoxic impurity furfural in furosemide and its tablets. By analyzing the measurement results and discussing the sources and control strategies of furfural, quality control of furosemide tablets can be achieved.
WU Jing-fang, CHEN Min-yu, MO Yun-si, LI Wei-ling, WU Liang-yong, DING Yi, LIU Yi
. Determination and evaluation of furfural in furosemide and its tablets *[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(8)
: 1387
-1393
.
DOI: 10.16155/j.0254-1793.2024-0279
[1] 赵思宁,杨慧,赵岩,等. 利尿药的临床应用及研究进展[J]. 疾病监测与控制,2022,16(4):331
ZHAO SN, YANG H, ZHAO Y. Clinical application and research progress of diuretics[J]. J Dis Monit Control, 2022, 16(4): 331
[2] 朱炯,王胜鹏,刘文,等.国家药品抽检药品质量提示数据分析与探讨[J]. 中国药事,2020,34(8):909
ZHU J, WANG SP, LIU W, et al. Analysis and discussion on the drug quality alert data of the drug sampling and testing[J]. Chin Pharm Aff, 2020, 34(8): 909
[3] 王翀,刘文,朱炯,等. 国家药品抽检中补充检验方法的建立情况分析[J]. 药物评价研究,2023,46(10):2061
WANG C, LIU W, ZHU J, et al. Analysis of establishment of supplementary testing methods in national drug sampling and testing[J]. Drug Eval Res, 2023, 46(10): 2061
[4] 郝帅帅. 呋塞米的合成工艺及有关物质的研究[D]. 连云港:江苏海洋大学,2022
HAO SS. Study on the Synthesis Technology of Furosemide and Related Substances[D]. Lianyungang: Jiangsu Ocean University, 2022
[5] 郭珊珊,陈娜,魏作君,等. Raney Ni 催化生物基糠醛还原胺化合成糠胺[J]. 合成化学,2022,30(1):35
GUO SS, CHEN N, WEI ZJ, et al. Synthesis of furfurylamine by reductive amination of biomass-based furfural over raney Ni gatalyst[J]. Chin J Syn Chem, 2022, 30(1): 35
[6] 赵亚男,何念平,韩淑娴,等. 呋塞米及其制剂中微量基因毒杂质的检测[J]. 药物分析杂志,2021,41(9):1534
ZHAO YN, HE NP, HAN SX, et al. Determination of trace genotoxic impurities in furosemide and its preparations[J]. Chin J Pharm Anal, 2021, 41(9): 1534
[7] 万君玥,陈华,尹婕. 化学药品中杂质的基因毒性评估策略以及相关分析方法研究进展[J]. 药物分析杂志,2022,42(4):557
WAN JY, CHEN H, YIN J. Strategies for genotoxicity assessment and advances in analytical techniques of impurities of chemical drugs[J]. Chin J Pharm Anal, 2022, 42(4): 557
[8] ICH M7(R2). Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk[S]. 2023
[9] 葛雨琦,叶晓霞,乐健,等. N-亚硝胺类基因毒性杂质毒性与检测方法研究进展[J]. 药物分析杂志,2020,40(1):83
GE YQ, YE XX, LE J, et al. Research progress on toxicity and detection methods of N-nitrosamines genotoxic impurities[J]. Chin J Pharm Anal, 2020, 40 (1): 83
[10] 郭常川,谭会洁,刘琦,等. 超高效液相色谱-静电场轨道阱高分辨质谱法测定硝苯地平中痕量基因毒性杂质[J]. 色谱,2022,40(3):266
GUO CC, TAN HJ, LIU Q, et al. Determination of trace genotoxic impurities in nifedipine by ultra high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry[J]. Chin J Chromatogr, 2022, 40 (3): 266
[11] 中华人民共和国药典2020年版. 四部[S]. 2020:527 ChP 2020. Vol Ⅳ[S]. 2020: 527
[12] Furfural: Cancer Test Summary[DB/OL]. National Library of Medicine, 2005[2019-04-6]. https://toxnet.nlm.nih.gov/cpdb/chempages/FURFURAL. html.
[13] MARTINDALE M. The Complete Drug Reference[M]. Vol. 36. London: The Pharmaceutical Press, 2009: 1292
[14] 王云,朱建伟. 化学合成原料药起始物料的选择原则[J]. 中国医药工业杂志, 2022, 53(5):728
WANG Y, ZHU JW. Principles for selection of starting materials for chemical synthetic API[J]. Chin J Pharm, 2022, 53(5): 728
[15] 国家食品药品监督管理局. 化学药品技术标准[EB/OL]. (2008-06-03)[2024-03-20]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20080603121101204.html.
China Food and Drug Administration. Technical Standards for Chemical Drugs[EB/OL]. (2008-06-03)[2024-03-20]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20080603121101204.html.
