目的:建立HPLC 法测定呋塞米及其制剂中微量基因毒杂质糠醛的检测方法,提高了呋塞米的质量控制要求。方法:采用十八烷基硅烷键合硅胶为填充剂的色谱柱,以磷酸溶液和乙腈为流动相,检测波长270 nm。结果:呋塞米及其制剂各国药典标准中报道的已知杂质对其检测均不干扰;杂质的检测下限为12 ng·mL-1;在0.04~4.088 μg·mL-1范围内线性关系良好,r2=1.000;呋塞米及其制剂中的平均回收率分别为99.8%(RSD=2.8%)、98.9%(RSD=0.9%)及100.9%(RSD=2.4%);呋塞米原料及其市售制剂中有0.003%~0.004% 的糠醛检出。结论:本方法专属性强、灵敏度高、准确性好,可用于呋塞米及其制剂中潜在基因毒杂质糠醛的有效检测,保证呋塞米制剂的有效性和安全性。
Objective: To establish an HPLC method for determining trace genotoxic impurities in furosemide and its preparations. Methods: The chromatographic column was filled with octadecylsilane bonded silica gel,with phosphoric acid solution and acetonitrile as mobile phase,and the detection wavelength was 270 nm. Results: The known impurities in the pharmacopoeia did not interfere with the detection. The detection limit of impurities was 12 ng·mL-1. The linearity between 0.04-4.088 μg·mL-1 was good,r2=1.000. The average recoveries of furosemide and its preparations were 99.8%(RSD=2.8%),98.9%(RSD=0.9%)and 100.9%(RSD=2.4%). There were 0.003%-0.004% furfural detected in furosemide and its commercial preparations. Conclusion: This method has high specificity,sensitivity and good accuracy,and can be used to detect furfural,a trace gene toxin impurity in furosemide and its preparations. This method ensures the efficacy and safety of furosemide preparations.
[1] 懒荣德,文开平. 呋塞米的应用现状[J]. 四川医学,1996,17(6):381
LAN RD,WEN KP.Application status of furosemide[J]. Sichuan Med Sci,1996,17(6):381
[2] 罗长荣,吕道海. 吸入呋塞米治疗支气管哮喘[J]. 中国医院药学杂志,2003,23(8):45
LUO CR,L DH. Treatment of bronchial asthma by inhalation of furosemide[J]. Chin J Hosp Pharm,2003,23(8):45
[3] 阮晓玲,郑项元,徐洁. 药物中基因毒性杂质分析方法的研究进展[J]. 中国药科大学学报,2016,47(3) :267
RUAN XL, ZHENG XY,XU J,et al.Research progress in the analysis of genotoxic impurities in drugs[J]. J China Pharm Univ, 2016,47(3) :267
[4] BOSCH ME,RUIZ AJ.Recent developments in analytical determination of furosemide[J]. J Pharm Biomed Anal,2008(48):519
[5] EP 9.0.[S]. 2012:2551
[6] Furfural :Cancer Test Summary[DB/OL]. National Library of Medicine,2005[2019-04-16]. https://toxnet.nlm.nih.gov/cpdb/chempages/FURFURAL.htmL
[7] Martindale M.The Complete Drug Reference.[M] Vol.36. Britain: The Pharmaceutical Press,2009:1292
[8] USP 40-NF 35. 40-NF 35.Vol[S]. 2017:4347
[9] 中华人民共和国药典2020 年版. 二部[S]. 2020:465
ChP 2020.Vol Ⅱ[S]. 2020:465
[10] JP17 Vol XⅦ.[S] 2017:970
[11] 么世英. 呋塞米片质量标准提高研究[J]. 中国药业,2017,26(4) :19
YAO SY .Improvement of quality standard for furosemide tablets[J]. China Pharm,2017,26(4):19
[12] 王峰,陶巧凤. HPLC 法测定呋塞米注射液中的有关物质及含量[J]. 药物分析杂志,2012,32(6):1081
WANG F,TAO QF.HPLC determination of furosemide injection and its related substance[J]. Chin J Pharm Anal,2012,32(6):1081
[13] 黄萍,刘萍 . HPLC法测定呋塞米片中有关物质 B[J]. 广州化工,2017, 45(15):151
HUANG P,LIU P.Determination of related compound B in furosemide tablets by HPLC[J]. Guangzhuo Chem Ind,2017,45(15):151
[14] SHINJI K,NOBUO Y.Identification of furosemide photodegradation products in water-acetonitrile mixture[J]. Chem Pharm Bull,2015 (63):617
[15] BROCH SC,ROMERO JE.Furosemide assay in pharmaceuticals by Micellar liquid chromatography:study of the stability of the drug[J]. J Pharm Biomed Anal,2000,23:803
