Objective: To investigate the correlation between the quality discrepancy of cefathiamidine for injection and the clinical adverse reaction. Methods: The data of national post market surveillance and clinical adverse reaction were collected. Multi-variances data analysis tools, for instance, single factor analysis of variance, multiple comparison, correlation analysis, linear regression, etc. were applied to explore the quality discrepancy of cefathiamidine for injection and the consequence on clinical safety. The analysis was focused on routine quality control parameters and crystal form. Results: Among all the quality control parameters, only impurity B was significantly correlated with the number of serious ADR reports, and its difference mainly came from sterilized sub-packaging and storage process. Moreover, there was a high fitting correlation between crystal form and impurity B with the correlation coefficient of 0.72. Mixed state of crystal A and crystal B was associated with high ADR frequency and crystal C form was reported low ADR frequency. It was assumed that crystal form and impurity B control was an important factor to reduce the ADR frequency. Conclusion: It would be possible to reduce the change of drug quality, especially impurity B, during the sterilized sub-packaging and storage process by optimize the crystallization process to obtain crystal C, so as to reduce the incidence of clinical ADR of cefathiamidine for injection.
QI Shu-ye, YIN Li-hui, ZHANG Dou-sheng, CHONG Xiao-meng, WANG Li-xin, ZOU Wen-bo, XU Ming-zhe
. Quality re-assessment of cefathiamidine for injection[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(12)
: 2219
-2226
.
DOI: 10.16155/j.0254-1793.2021.12.21
[1] 薛峰,李耘,吕媛,等.头孢硫脒最低抑菌浓度及其影响因素研究[J].中国临床药理学杂志, 2018, 34(1): 25
XUE F, LI Y, LÜ Y, et al. Study on minimum inhibitory concentrations and its influence factors of cefathiamidine [J].Chin J Clin Pharmacol, 2018, 34(1): 25
[2] 国家药品不良反应监测中心. 药品不良反应信息通报—警惕注射用头孢硫脒引起的过敏性休克及儿童用药风险[J].中国药物警戒, 2016, 13(5): 316
National Center for ADR Monitoring. Adverse drug reaction information bulletin-beware of anaphylactic shock caused by cefathiamidine for injection and the risk of drug use in children[J].Chin J Pharmacovigil, 2016, 13(5): 316
[3] 赵金龙,陈国铭,钟晓莹,等.头孢硫脒不良反应的Meta分析[J].中国抗生素杂志, 2018, 43(6): 750
ZHAO JL, CHEN GM, ZHONG XY, et al. Meta-analysis of adverse drug reactions of cefathamidine[J].Chin J Antibiot, 2018, 43(6): 750
[4] 刘学斌,许淑文,邓泽民.头孢硫脒纯化新方法[J].中国抗生素杂志, 2007, 32(10): S1
LIU XB, XU SW, DENG ZM. A new purification method of crude cefathiamidine[J].Chin J Antibiot, 2007, 32(10): S1
[5] 刘玲,林顺权,袁晓,等.头孢硫脒新杂质的制备及结构解析[J].中国抗生素杂志, 2019, 44(6): 706
LIU L, LIN SQ, YUAN X, et al. Preparation and structure analysis of new cefathiamidine impurities[J].Chin J Antibiot, 2019, 44(6): 706
[6] 吕萌,陈海燕.头孢硫脒不良反应文献分析及原因探讨[J].中国医院药学杂志, 2017, 37(16): 1638
LÜ M, CHEN HY. Literature analysis and reason investigation for adverse reaction of cefathiamidine[J].Chin J Hosp Pharm, 2017, 37(16): 1638
[7] QI SY, TIAN Y, ZOU WB, et al. Characterization of solid-state drug polymorphs and real-time evaluation of crystallization process consistency by near-infrared spectroscopy[J].Front Chem, 2018, 6: 506
[8] 李亚卿,刘亚林,乔俊华,等.注射用头孢呋辛钠原粉结晶工艺优化[J].煤炭与化工, 2018, 41(11): 148
LI YQ, LIU YL, QIAO JH, et al. Optimization of crystallization process of cefuroxime sodium for injection raw powder[J].Coal Chem Ind, 2018, 41(11): 148
[9] 黄美英,祁俊生,李军.头孢唑肟钠制备条件最优化研究[J].中国抗生素杂志,2009, 34(12): 726
HUANG MY, QI JS, LI J. Study on the optimal conditions for preparation of ceftizoxime sodium[J].Chin J Antibiot, 2009, 34(12):726
[10] 龚俊波,侯静美,刘胜,等.头孢羟氨苄单水合物反应结晶工艺优化[J].中国抗生素杂志, 2012, 37(4): 280
GONG JB, HOU JM, LIU S, et al. Optimization of cefadroxil monohydrate reactive crystallization process[J].Chin J Antibiot, 2012, 37(4): 280
[11] 李慧芬,乔俊华,蔡秋琴, 等. 头孢曲松钠结晶工艺研究[J].河北化工, 2010, 33(12): 36
LI HF, QIAO JH, CAI QQ, et al. Researches in ceftriaxone sodium crystallization process [J].Hebei Chem Ind, 2010, 33(12): 36
[12] 崇小萌,田冶,姚尚辰,等.注射用头孢硫脒聚合物检测方法比较及聚合物杂质分析[J].中国新药杂志, 2021, 30(14): 1334
CHONG XM, TIAN Y, YAO SC, et al. Comparison of different polymer detection methods and analysis of polymer impurities of cefathiamidine for injection[J].Chin J New Drugs, 2021, 30(14): 1334
[13] 项晓娟,全红.浅谈非临床研究与ADR监测[J].中国药事,2004, 18(8): 479
XIANG XJ, QUAN H. A preliminary discussion on non-clinical study and ADR monitoring[J].Chin Pharm Aff, 2004, 18(8): 479
[14] 游翠玉,许晓丽,李莎,等.某院140例严重药品不良反应/事件报告分析[J].中国药物警戒, 2020, 17(9): 617
YOU CY, XU XL, LI S, et al. 140 cases of severe adverse drug reactions/events in a hospital[J].Chin J Pharmacovigil, 2020, 17(9): 617
[15] 黄斌学,姚永全,傅玉新.29例严重药品不良反应报告分析[J].中国医药导报, 2009, 21(6):142
HUANG BX, YAO YQ, FU YX. Analysis of 29 serious ADR cases[J].Chin Med Her, 2009, 21(6):142
