Degradation of micropollutant cephalexin by ultraviolet (UV) and assessment of residual antimicrobial activity of transformation products

Abstract

Cephalexin (CEX) is an antibiotic commonly used to treat bacterial infections in humans and animals. However, it can be considered a micropollutant. Thus, this study evaluated the degradation of CEX using ultraviolet irradiation (UV-C) and analyzed the by-products as well as their residual antimicrobial activity. A reactor with a mercury vapor lamp was used for the degradation. Irradiated CEX solution were collected over a period of 4 h and analyzed by High Performance Liquid Chromatography coupled with Mass Spectrometry. For the residual antimicrobial activity the susceptibility test was performed by broth microdilution against Staphylococcus aureus and Escherichia coli microorganisms. It was found that CEX, after treatment, generated a metabolite with a mass of 150 m/z in 15 min, and a 4- and 8-fold increase in the minimum inhibitory concentration of the drug against S. aureus and E. coli, could be observed, respectively, after 20 min. Therefore, this treatment proved to be effective in the degradation of CEX, being able to degrade 81% of the initial molecule of the drug in 20 min. Furthermore, the antimicrobial activity of the CEX solution decreased as the irradiation time increased, indicating loss of antimicrobial function of the initial CEX molecule and the resulting by-products.

Molecular Structure and Antibacterial Activity of Degradation Products from Cephalexin Solutions Submitted to Thermal and Photolytic Stress

“…The proposed fragmentation pattern leading to these lactam species is shown in Scheme 2, where the main steps in the pathway are decarboxylation and oxidation reactions. Among major mass peaks throughout the spectrum, we observed several fragments consistent with byproducts already identified for cephalexin subjected to forced degradation [26,33,38] . For example, the peak m/z 214 can be assigned to the so‐called impurity B (mass=214.2, Scheme 2 #3 ) [38] and the peak m/z 304 is compatible with a degradation product formed from the decarboxylation of the native cephalexin (Scheme 2, #2 ).…”

“…Very interesting studies have demonstrated the potential of ultraviolet radiation for remediation of micropollutants derived from cephalexin and other antibiotics. [16,26,42] However, these studies rely on the use of UVC light, which is a virtually nonexistent component in sunlight reaching the earth's surface. [43] In this context, the findings presented here demonstrate that irradiation of sunlight on cephalexin improperly discarded in the environment likely produces byproducts with the capacity to substantially affect the balance of the microbiota.…”

“…Among major mass peaks throughout the spectrum, we observed several fragments consistent with byproducts already identified for cephalexin subjected to forced degradation. [26,33,38] For example, the peak m/z 214 can be assigned to the so-called impurity B (mass = 214.2, Scheme 2 #3) [38] and the peak m/z 304 is compatible with a degradation product formed from the decarboxylation of the native cephalexin (Scheme 2, #2). The spectrum also reveals a few peaks that can be ascribed to oxidized forms of the antibiotic; namely, cephalexin sulfoxide and cephalexin sulfone byproducts can be attributed to m/z values at 364 and 380, respectively (Scheme 2, compounds #4 and #5).…”

“…A part of these reports are clinical studies investigating bacterial resistance to beta‐lactam antibiotics, a serious public health problem worldwide [18–20] . On the other hand, given that the indiscriminate use of antibiotics has led to real risks to the ecosystem balance, there is also a fairly high relatively of recent studies related to the search for strategies to detect cephalexin in the environment and the development of new strategies aimed at its remediation [12,21–26] . In addition, an important fraction of these studies focuses on the development of methods for quality control in drug production [17,20,27–29] .…”

“…[18][19][20] On the other hand, given that the indiscriminate use of antibiotics has led to real risks to the ecosystem balance, there is also a fairly high relatively of recent studies related to the search for strategies to detect cephalexin in the environment and the development of new strategies aimed at its remediation. [12,[21][22][23][24][25][26] In addition, an important fraction of these studies focuses on the develop- ment of methods for quality control in drug production. [17,20,[27][28][29] In this context, the knowledge of byproducts generated from the degradation of cephalexin becomes relevant since it brings potentially useful information both for the improvement of processes related to drug production and to the management environmental waste resulting from the degradation of these species.…”