Analysis of impurity profile of levofloxacin lactate and sodium chloride injection

doi:10.19803/j.1672-8629.2022.05.11

Abstract

Abstract: Objective To establish the impurity profile of levofloxacin lactate and sodium chloride injection, and predict the toxicity of the identified impurities. Methods The impurity profile of levofloxacin lactate and sodium chloride injection was studied according to the inspection method of levofloxacin related substances in ChP 2015 edition. Together with the prescription and process, the source and attribution of impurity were analyzed and the influence of metal complexing agent in the prescription on the impurities of the product was studied. At the same time, ADME/T property prediction software was used to predict the toxicological properties of the known impurities. Results Eight main impurities were found in levofloxacin lactate and sodium chloride injection, four degradation impurities B, E, F, G and four unknown process impurities, the impurities in preparations mainly come from raw materials, and key impurity E was key factor in raw materials producing control, impurities G, the light degradation impurity, was the key factor for quality control. All impurities were toxic with different levels. Conclusion The establishment of impurity profile of levofloxacin lactate can provide a data reference for consistency evaluation of levofloxacin lactate and sodium chloride injection.

Key words: levofloxacin lactate, impurity profile, toxicological property, consistency evaluation

CLC Number:

R917

XIAO Qinqin, CHEN Xi, DUAN Hexiang, ZHANG Yinhua, LIU Xuping, WANG Chen. Analysis of impurity profile of levofloxacin lactate and sodium chloride injection[J]. Chinese Journal of Pharmacovigilance, 2022, 19(5): 527-531.

References

[1] LI Y, ZHU M.Analysis of 134 cases of levofloxacin sodium chloride injection induced adverse effects[J]. Journal of North Pharmacy(北方药学), 2018, 15(8): 178-179.
[2] GUO YL.Analysis and safety assessment of 76 cases of adverse drug reaction reports of Levofloxacin Lactate Injection[J]. Drug Evaluation Research(药物评价研究), 2016, 39(4): 594-597.
[3] XIE Q, DONG N, LIU Y, et al.A case of severe anaphylactic shock caused by levofloxacin lactate and sodium chloride injection[J]. Chinese Journal of Hospital Pharmacy(中国医院药学杂志), 2015, 35(6): 563.
[4] HAN XP, CHEN HH, LIU XP.A case of anaphylactic shock caused by levofloxacin lactate injection[J]. World Latest Medicine Information(世界最新医学信息文摘), 2018, 18(90): 185.
[5] DAI SH, FANG BQ, CHEN CM.A case of photoallergy induced by Levofloxacin[J]. Journal of Medical theory and practice(医学理论与实践), 2021, 34(1): 117-118.
[6] ORMAN ES, CONJEEVARAM HS, VUPPALANCHI R, et al.Clinical and histopathologic features of fluoroquinolone-induced liver injury[J]. Clin Gastroenterol Hepatol, 2011, 9(6): 517-523.
[7] ZHENG YJ, ZHANG RP, GAO Y, et al.Impurity analysis and quality evaluation for commercial levofloxacin formulations using LC-MS/ MS method[J]. Acta Pharmaceutica Sinica(药学学报), 2016, 51(3): 444-449.
[8] WU JP, CHEN Q, LIU S.Quality assessment of domestic levofloxacin tablets[J]. Chinese Journal of Antibiotics(中国抗生素杂志), 2020, 45(3): 234-240.
[9] W ANG S, Z HOU L L, M A Y Y, e t a l. D etermination o f r elated substances in levofloxacin hydrochloride and sodium chloride injection by HPLC[J]. Strait Pharmaceutical Journal(海峡药学), 2020, 32(6): 52-55.
[10] European Pharmacopoeia 10.0 Pharmacopoeia 10.0[S]. Strasbourg: European directorate for the quality of medicines, 2020.
[11] The British Pharmacopoeia2019[S]. British Pharmacopoeia Commission: 2019(Ⅱ): 445-446.
[12] The United States Pharmacopoeia 42th Edition[S]. Rockuille MD: The United States Pharmacopoeia Convention Inc, 2018.
[13] HU CQ.Rethought on quality consistency evaluation/re-evaluation for domestic antibiotic injections[J]. Chinese Journal of Antibiotics(中国抗生素杂志), 2019, 44(3): 281-288.
[14] HU CQ, ZHANG X.Current situation and the trend in impurity profiling of chemical drugs[J]. Acta Pharmaceutica Sinica(药学学报), 2019, 54(12): 2214-2231.
[15] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People's Republic of China[S]. (Volume Ⅱ, 2015). Beijing: Chemical Industry Press, 2015.
[16] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People's Republic of China[S]. (Supplement in 20 04, 20 0 0). Beijing: Chemical Industry Press, 2004.
[17] LIU F, ZHANG Y, WANG WJ.Detemination of descarboxyl levofloxacin by HPLC[J]. Journal of Pharmaceutical Research(药学研究), 2016, 35(8): 463-465.