Objective: To establish a method to determination of the related substances and polymer impurities in cefminox sodium for injection. Method: Cefminox sodium was degraded in high temperature to prepare degradation solution. An RP-HPLC method for the related substances analysis was established with a Kromisil C18 column (250 mm×4.6 mm, 5 μm), using 10 mmol · L-1 phosphate buffer solution (pH 2.0)-acetonitrile (98∶2) (A)-acetonitrile (B) with gradient elution at a flow rate of 1.0 mL · min-1. The column temperature was maintained at 25 ℃, the detection wavelength was set at 254 nm, and the injection volume was 20 μL. The specificity of RP-HPLC method and identification of unknown impurities was researched by 2D HPLC-MS/MS. Results: 14 main impurities were characterized in the degradation solution, including 3 cefminox dimmers and isomers which were characterized firstly. The impurities were determined in 7 batches of samples by principal component self-control with correction factor, the contents of impurity 3 were 0.01%-0.13%, the contents of impurity 4 were 0.10%-0.16%, the contents of impurity 5 were 0.02%-0.07%, the contents of impurity 6 were 0.04%-0.07%, the contents of polymer impurities were 0.03%-0.06%, the maximum single impurity contents were 0.01%-0.03%, while the total impurity contents were 0.28%-0.63%. Conclusion: Cefminox degradation solution in high temperature can be used to identify related impurities and polymer peaks as the systematic suitability testing solution. The RP-HPLC method was suitable for related substances as well as polymer impurities in cefminox sodium for injection. This work provides useful information for the quality control of cefminox sodium, which can contribute to establishment of reasonable impurity limits.
DING Ying
,
WEN Hong-liang
,
LE Jian
,
LIU Hao
,
LIAN Xiang-jin
. Analysis of the related substances in cefminox sodium for injection*[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(1)
: 125
-134
.
DOI: 10.16155/j.0254-1793.2024-0403
[1] NOJIRI T, FUJIMOTO E, BABA T, et al.Fundamental and clinical studies on cefminox sodium in the field of oral surgery[J]. Oral Ther Pharmacol, 2010, 8(2): 143
[2] 顾金萍,于健. 头孢米诺钠注射液抗感染疗效的临床评价[J]. 中国现代药物应用,2009,3(2): 144
GU JP, YU J.Clinical evaluation of the anti infective efficacy of cefminor sodium injection[J]. Chin J Mod Appl Pharm, 2009, 3(2): 144
[3] 陈书云,班建平. 注射用头孢米诺钠合理用药临床分析[J]. 中国社区医师(医学专业),2011,13(11): 26
CHEN SY, BAN JP.Clinical analysis of rational use of ceftriaxone sodium for injection[J]. Chin Comm Doct, 2011, 13(11): 26
[4] 白士先. 静脉滴注头孢米诺钠致全身皮疹并支气管哮喘急性发作1例[J]. 中国医院用药评价与分析,2014,14(5): 480
BAI SX.One case of acute exacerbation of systemic rash and bronchial asthma caused by intravenous infusion of cefminor sodium[J]. Eval Anal Drug Use Hosp China, 2014, 14(5): 480
[5] 王彩华. 头孢米诺钠注射剂致血小板减少1例[J]. 中国药师,2015,18(9): 1559
WANG CH.One case of thrombocytopenia caused by ceftriaxone sodium injection[J]. China Pharm, 2015, 18(9): 1559
[6] 龙敏,陈蓉,王颖. 头孢米诺致药品不良反应文献分析[J]. 中国药房,2011,22(22): 2077
LONG M, CHEN R, WANG Y.Analysis of adverse drug reactions induced by cefminox[J]. China Pharm, 2011, 22(22): 2077
[7] 刘朋,刘治军,王芙荣. 105例静脉输注头孢米诺钠不良反应的文献分析[J]. 首都医药,2011,18(24): 34
LIU P, LIU ZJ, WANG FR.Literature analysis of adverse reactions to intravenous infusion of cefminor sodium in 105 cases[J]. Cap Med, 2011, 18(24): 34
[8] 李兵,肖甜甜. 高效分子排阻色谱法测定头孢米诺钠聚合物的含量[J]. 中国医药指南,2013,11(26): 344
LI B, XIAO TT.Determination of the polymers in cefminox sodium by HPSEC[J]. Guide China Med, 2013, 11(26): 344
[9] 于涵光,徐亮. 注射用头孢米诺钠中有关物质HPLC检测方法的建立与验证[J]. 天津医科大学学报,2021,27(5): 529
YU HG, XU L.Development and validation of HPLC for determination of related substances in cefminox sodium for injection[J]. J Tianjin Med Univ, 2021, 27(5): 529
[10] XU Y, WANG DD, TANG L.Separation and characterization of unknown impurities and isomers in cefminox sodium and study of the forming mechanisms of impurities by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry[J]. J Chromatogr Sci, 2019, 57(3): 204
[11] 胡昌勤. β-内酰胺类抗生素聚合物杂质控制策略的形成与发展[J]. 中国新药杂志,2020,29(11): 1231
HU CQ.Impurity control strategy of β-lactam antibiotics polymer: the formation and development[J]. Chin J New Drugs, 2020, 29(11): 1231
[12] 李进,姚尚辰,尹利辉. 盐酸头孢甲肟原料及制剂的聚合物杂质分析[J]. 药物分析杂志,2021,41(1): 169
LI J, YAO SC, YIN LH.Analysis of polymer impurities in cefuroxime hydrochloride raw materials and preparations[J]. Chin J Pharm Anal, 2021, 41(1): 169
[13] 李进,姚尚辰,尹利辉. 头孢噻肟钠原料的聚合物杂质分析[J]. 中国抗生素杂志,2020,45(9): 883
LI J, YAO SC, YIN LH.Analysis of polymer impurities in cefotaxime sodium raw materials[J]. Chin J Antibiot, 2020, 45(9): 883
[14] 胡昌勤,蒋煜,张靖溥. 对β-内酰胺抗生素中微量不稳定杂质研究策略与方法的思考[J]. 中国新药杂志,2013,22(1): 9
HU CQ, JIANG Y, ZHANG JP.Reflection on strategy and methods on trace unstable impurities of β-lactam antibiotics[J]. Chin J New Drugs, 2013, 22(1): 9
[15] 徐雨. 基于二维色谱-质谱平台的头孢菌素类药物中杂质分析系统建立及机理研究[D]. 杭州: 浙江工业大学,2020
XU Y.Establishment of Impurity Analysis System for Cephalosporins Based on Two-dimensional Liquid Chromatography-Mass Spectrometry Platform and Research on Their Mechanism[D]. Hangzhou: Zhejiang University of Technology, 2020
[16] 胡昌勤,张夏,李进. 头孢菌素的聚合物分析[J]. 中国抗生素杂志,2022,47(3): 221
HU CQ, ZHANG X, LI J.Analysis of polymers of cephalosporins[J]. Chin J Antibiot, 2022, 47(3): 221
[17] 张强,廖工铁. 头孢类抗生素在水溶液中的聚合[J]. 药学学报,1996,31(4): 306
ZHANG Q, LIAO GT.Polymerization of cephalosporins in aqueous solution[J]. Acta Pharm Sin, 1996, 31(4): 306
[18] 胡昌勤,王晨,冯艳春,等. 一种头孢米诺钠晶体及其制备方法与应用: 中国,CN201310492849.0[P].2014-02-19
HU CQ, WANG C, FANG YC, et al. Cefminox Sodium Crystal as well as Preparation Method and Application Thereof: China, CN201310492849.0[P].2014-02-19
[19] 伍启章. 青霉素类抗生素二聚体的研究[D]. 北京: 中国食品药品检定研究院,2019
WU QZ.Research on Dimers of Penicillin Antibiotics[D]. Beijing: National Institutes for Food and Drug Control, 2019
