Stability of Metronidazole and Its Complexes with Silver(I) Salts under Various Stress Conditions.

Małgorzata Starek,Joanna Chebda,Monika Dąbrowska,Dominik Żyro,Justyn Ochocki

doi:10.3390/molecules26123582

Małgorzata Starek, Joanna Chebda + Show 3 more

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https://doi.org/10.3390/molecules26123582

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Abstract

Metronidazole is a drug widely used in the prevention and treatment of bacterial infections. Due to its possibility of the formation of stable metal complexes, it was decided to broaden its activity spectrum by introducing the silver(I) coordination compounds i.e., [Ag(MTZ)2NO3] and [(Ag(MTZ)2)2]SO4, which have significant antibacterial properties. The paper presents a description of a new qualitative and quantitative analysis of metronidazole in bulk and possible pharmaceutical preparations by thin-layer chromatography with densitometric detection. Optimal separation conditions were selected, and the analytical procedure was validated according to the ICH guidelines. The obtained data indicate that the method is sufficiently sensitive, precise, and accurate. The stability of the metronidazole solutions obtained from tablets, pure metronidazole, and its silver(I) complexes was tested. The research was carried out in various environments, at different temperatures, in H2O2 solution, and during exposure to radiation (UV, sunlight). The greatest degradation was found in the alkaline environment and at higher temperatures. The silver(I) complexes exhibited relatively high stability under analyzed conditions that are higher than standard metronidazole solutions and tablets. The observations were confirmed by the kinetic and thermodynamic analysis. The described studies of new metronidazole silver(I) complexes increase the potential for their application in infections both in humans and animals.

Highlights

Metronidazole (MTZ, 2-metyl-5-nitro-1H-imidazole-1-ethanol; Figure 1) is a derivative of 5-nitroimidazole
We described the synthesis of the silver(I) complex with Metronidazole standard substance (MTZ) and the study of its cytotoxic activity against Balb/c3T3, HepG2, PANC-1, and 1.2B4 cells [15,16]
Silicagel 60F254 Thin layer chromatography (TLC) chromatography plates and the mobile phase that consisted of ethyl acetate + methanol + ammonia 25%

Summary

Introduction

Metronidazole (MTZ, 2-metyl-5-nitro-1H-imidazole-1-ethanol; Figure 1) is a derivative of 5-nitroimidazole. It exhibits the greatest activity against anaerobic Gram-negative bacteria but has no activity against aerobic bacteria [1]. It is used to treat infections caused by most anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Entamoeba histolytica, or Giardia lamblia It is used in the therapy of trichomoniasis of the genitourinary system, amoebiasis, giardiasis, treatment of infections such as Clostridium, Eubacterium, Bacteroides, Fusobacterium, and Gardnerella vaginalis. It is widely used in the prevention of post-operative infections and therapeutically in conditions caused by anaerobic bacteria, such as sepsis, pneumonia, brain abscess, peritonitis, osteomyelitis, puerperal fever, or bedsores and ulcers of the lower limbs [2]. Free nitro radicals are formed, which damage the DNA chain and lead to the destruction of the microbial cell [4]

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