Do dietary interventions exert clinically important effects on the bioavailability of ß-lactam antibiotics? A systematic review with meta-analyses.

BACKGROUND: Managing drug-food interactions may help to achieve the optimal action and safety profile of ß-lactam antibiotics. METHODS: We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 ß-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. RESULTS: Eighteen of 25 ß-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed ß-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). CONCLUSIONS: Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.

Improving antibiotic removal and anaerobic digestion performance of discarded cefradine pellets through thermo-alkaline pretreatment.

Discarded cefradine pellets (DCP) as the hazardous wastes contain lots of bioavailable sucrose. Anaerobic digestion (AD) may be a promising technology for treating DCP, achieving dual goals of waste treatment and resource recovery. However, high concentration of cefradine will inhibit the AD process. This study applied thermo-alkaline pretreatment (TAP) to remove cefradine and improve the AD performance of DCP. Around 95% cefradine could be degraded to different intermediate degradation products (TPs) in TAP at optimal condition, and hydrolysis and hydrogenation were the main degradation pathways. Quantitative structure-activity relationship analysis indicated that the main TPs exhibited lower toxicity than cefradine, and DCP residues after TAP were almost not toxic to E. coli K12 and B. subtilis growth by antibacterial activity analysis. Therefore, TAP promoted the biomethane yield in AD of DCP residues (274.74 mL/g COD), which was 1.91 times that of control group. Besides, compared to control group, final cefradine concentrations in liquids and sludge were significantly decreased in AD system with TAP, lowering environmental risk and indicating stronger prospect for process application. Microbiological analysis revealed that acidogens (Macellibacteroides, Bacteroides), syntrophs (Syntrophobacter, Syntrophorhabdus), and acetoclastic Methanosaeta were enriched in AD system with TAP, which contributed to improving AD performance of DCP.

Solar-driven persulfate degradation of caffeine and cephradine in synthetic human urine.

Urine source separation, as an innovative concept for the reuse of microlevel nutrients in human urine, has drawn increasing attention recently. Consequently, removing coexisting pharmaceuticals in urine is necessary for further reuse. This study is the first to apply the solar-driven persulfate process (Solar/PS) to the investigation of cephradine (CFD) and caffeine (CAF) degradation in synthetic human urine. The results showed that significantly more degradation of CFD and CAF occurs with the Solar/PS process than with persulfate oxidation and direct sunlight photolysis, respectively. The generated reactive species ·OH, SO4·-, O2·- and 1O2 were identified in the Solar/PS process. While SO4·- played a dominant role at pH 6, it played a minor role at pH 9 due to the lower amount generated under alkaline conditions. The presence of chloride and ammonia negatively impacted the photodegradation of both compounds. In contrast, bicarbonate exhibited no effect on CAF but enhanced CFD degradation owing to its amino-acid-like structure, which has a higher reactivity toward CO3·-. Although total organic carbon (TOC) was partially mineralized after 6 h of operation, no Microtox® toxicity was observed.

Monocarboxylate Transporter 13 (MCT13/SLC16A13) Functions as a Novel Plasma Membrane Oligopeptide Transporter.

SLC16A13, which encodes the monocarboxylate transporter 13 (MCT13), is a susceptibility gene for type 2 diabetes and is expressed in the liver and duodenum. Some peptidase-resistant oligopeptides are absorbed in the gastrointestinal tract and affect glycemic control in the body. Their efficient absorption is mediated by oligopeptide transporter(s) at the apical and basolateral membranes of the intestinal epithelia; however, the molecules responsible for basolateral oligopeptide transport have not been identified. In this study, we examined whether MCT13 functions as a novel basolateral oligopeptide transporter. We evaluated the uptake of oligopeptides and peptidomimetics in MCT13-transfected cells. The uptake of cephradine, a probe for peptide transport system(s), significantly increased in MCT13-transfected cells, and this increase was sensitive to membrane potential. The cellular accumulation of bioactive peptides, such as anserine and carnosine, was decreased by MCT13, indicating MCT13-mediated efflux transport activity. In polarized Caco-2 cells, MCT13 was localized at the basolateral membrane. MCT13 induction enhanced cephradine transport in an apical-to-basal direction across Caco-2 cells. These results indicate that MCT13 functions as a novel efflux transporter of oligopeptides and peptidomimetics, driven by electrochemical gradients across the plasma membrane, and it may be involved in the transport of these compounds across the intestinal epithelia.

Graphene oxide reinforced biopolymeric (chitosan) hydrogels for controlled cephradine release.

In the current study, chitosan, poly (N-vinyl-2-pyrolidone) and polyamidoamine based hydrogels were prepared by Solution Casting Method using different quantity of graphene oxide (GO) for controlled cephradine (CPD) release. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis, scanning electron microscope and atomic force microscopy. FTIR results endorsed the presence of particular functionalities and developed interfaces in hydrogels. The thermal stability was directly proportional to the amount of GO. Antibacterial activity was investigated against gram-negative bacteria resultantly; CAD-2 exhibited maximum bactericidal activity against Escherichia coli and Psuedomonas aeruginosa. In addition, in-vitro biodegradation was examined in phosphate buffer saline solution and proteinase K for 21 and 07 days respectively. The maximum swelling was exhibited by CAD-133777 % in distilled water that was governed by quasi-Fickian diffusion. The swelling volumes were inversely proportional to the amount of GO. In the same way, pH sensitive CPD release was detected by UV visible spectrophotometer that followed zero order and Higuchi models. However, in 4 h, 89.4 % and 83.7 % of CPD was released in PBS and SIF solution correspondingly. Therefore, the chitosan-based biocompatible and biodegradable hydrogel platforms offered substantial potential for the controlled CPD release in medico-biological applications.

Preparation and biological evaluation of radio conjugated cephradine complex for infection imaging.

Antimicrobial resistance is a major challenge in the field and threat to human life. Many patients are suffering from cancer, infection and other diseases simultaneously. Therefore, early detection of infection can lead to treatment of these patients with an appropriate antibiotic. Hence, the development of a specific imaging molecule can increase the speed of infection analysis and thereby application of proper antibiotic. The present work involves the optimization of labelling conditions for an antibiotic of cephalosporin family, cephradine with technetium-99m (99mTc) and establishment of quality control tests. Labelling of cephradine was also determined by applying MALDI-TOF mass spectrometry. Evaluation of in vitro binding with S. aureus bacteria was carried out. Animal model was used to conduct in vivo binding studies. For this, infected animals were injected with the radiolabelled ligand and images were captured by Gamma camera, to observe target to non-target uptake of radiolabelled complex. Furthermore, we optimized various parameters to achieve best labelling efficacy and stability of cephradine. Our results show that cephradine can be used as potential infection imaging agent for advanced clinical care.

Insight on the heterogeneously activated H2O2 with goethite under visible light for cefradine degradation: pH dependence and photoassisted effect.

The iron mineral-catalyzed degradation of cephalosporin antibiotics with H2O2 occurs ubiquitously in nature. Despite numerous studies, the effects of environmental conditions on reactive species production and degradation processes of cephalosporins remain unclear. Here, we report the iron mineral of goethite as the efficient and heterogenous catalyst for the degradation of cefradine (CRD) via H2O2 activation under different conditions involving pH and visible light irradiation. Results show that the CRD removal rate is highly dependent on pH and visible light irradiation. Interestingly, when the pH ranges from 4.0 to 7.0, the degradation intermediates of CRD under dark are the same as under visible light conditions in the goethite/H2O2 system. And, the ratio of CRD degradation rate constant (kLight/kDark) reaches a maximum at pH 5.0, suggesting that CRD existing as zwitterion species is preferable for its removal with photoassistance. The mechanism investigation reveals that both •OH and ≡[FeIVO]2+ oxidants are generated during the reaction process, and •OH is the major oxidant at acidic pH, while ≡[FeIVO]2+ is more likely to be formed with photoassistance at near-neutral pH. According to UPLC-MS/MS analysis, CRD degradation likely happens via hydrogen atom abstraction from cyclohexadienyl by •OH, thioether and olefin oxidation by ≡[FeIVO]2+, and FeIII-catalyzed hydrolytic cleavage of ß-lactam ring. These findings highlight the vital roles of pH and photoassistance in the heterogeneously activated H2O2 with goethite for CRD degradation.

Comparative efficacy of cephradine-loaded silver and gold nanoparticles against resistant human pathogens.

Infections caused by drug-resistant bacteria are major health concerns worldwide. We successfully synthesized cephradine gold nanoparticles (Ceph-Au NPs) and cephradine silver nanoparticles (Ceph-Ag NPs) and compared their efficacy against resistant human pathogens. X-Ray diffraction (XRD), Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) results showed that average particle size of Ceph-Au NPs and Ceph-Ag NPs were 7 and 12 nm, respectively. Fourier Transform Infra-red spectroscopy (FTIR) spectra revealed the conjugation of -NH2 and -OH functional moieties with the nanoparticle (NP) surfaces. These NPs significantly inhibited the biofilm of Streptococcus mutans (S. mutans) and methicillin-resistant Staphylococcus aureus (MRSA) in the range of 61.25-250 µg/mL. Ceph-Au NPs are more active than Ceph-Ag NPs and can be used to treat the diseases associated with MRSA and S. mutans.

Screening of Antibacterial Efficacy of Chitosan Encapsulated Probiotics (Lactococcus lactis and Lactobacillus curvattus) against Clinical Bacterial Pathogens.

Probiotics frontier in depressing the clinical bacterial pathogens to avoid multidrug resistance phenomenon. The present study aimed to determine the antibacterial efficiency of chitosan encapsulated probiotics isolated from buffalo milk samples against clinical bacterial pathogens. The Agar well method was used for antibacterial activity. Lactococcus lactis (A) and Lactobacillus curvattus (B) were isolated from fresh buffalo milk samples, identified via culturing media, Gram's staining, biochemical tests, and antibiogram analysis. Encapsulation of probiotics was carried out using chitosan and was characterized via a scanning electron microscope. Antibiogram analysis elicit that L. lactis culture (A1) was highly sensitive to chloramphenicol (17.66±0.47 mm), tobramycin (15.33±0.47 mm), and ciprofloxacin (12.33±0.47 mm) and resistant against tetracycline, Penicillin G, Erythromycin, Amoxycillin, Ceftriaxone, Cephalothin, and Cephradine, while L. curvattus culture (B1) was affected by Ceftriaxone (18.67±0.47 mm), Amoxycillin (14.33±0.94 mm), Cephalothin (13.67±0.47 mm), Erythromycin (13.33±0.47 mm), Penicillin G (12.67±0.47 mm), Cephradine (10.33±0.47 mm), and Chloramphenicol (9.67±0.47 mm) and resistant against tetracycline, Tobramycin, and Ciprofloxacin. Antibacterial efficacy of non-encapsulated probiotic cultures was significant and maximum inhibition of bacterial were recorded compared to their cellular components. SEM of encapsulated probiotics revealed that they were successfully covered with a chitosan protective layer and could be effective as bio-preservatives due to being slowly released at the target site. The current study concluded that L. lactis, L. curvattus, and their cellular components have a significant bactericidal effect against infectious pathogens and could be used as a potential therapeutic drug against infectious diseases.

Synthesis, characterization, SAR, antioxidant, anti-acetylcholinesterase and anti-butyrylcholinesterase activities of cephradine Schiff bases.

The objective of this study was to deal with the evaluation of 7-(2-(benzylideneamino)-2-(cyclohexa-1,4-dienyl)acetamido)-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid based schiff bases as a new class of enzyme inhibitors. In this connection, a series of Schiff bases of cephradine with substituted aromatic aldehydes was synthesized and characterized using FTIR, 1HNMR and 13CNMR. The in-vitro biological activities including free radical scavenging potential using DPPH assay, acetyl cholinesterase and butyryl cholinesterase inhibition potential were evaluated. Two compounds of the series 1g and 1h were found to be active against AChE whereas no derivative was active against BChE while the whole series showed excellent 1, 1-diphenyl-2-picrylhydrazyl scavenging activity. All the synthesized compounds were found to be non-toxic and present passive gastrointestinal absorption. Furthermore, the study suggests that the synthesized cephradine derivatives exhibit inhibitory potential against different biologically relevant enzyme targets.

The use of first-generation cephalosporin antibiotics, cefalexin and cefradine, is not associated with induction of simulated Clostridioides difficile infection.

OBJECTIVES: The use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections. Here, the effects of two first-generation cephalosporins, compared with a third-generation cephalosporin, on the human microbiota were investigated and their propensity to induce simulated CDI. METHODS: Three in vitro chemostat models, which simulate the physiochemical conditions of the human colon, were seeded with a human faecal slurry and instilled with either narrow-spectrum cephalosporins, cefalexin and cefradine, or a broad-spectrum cephalosporin, ceftriaxone, at concentrations reflective of colonic levels. RESULTS: Instillation of cefalexin was associated with reduced recoveries of Bifidobacterium and Enterobacteriaceae; however, Clostridium spp. recoveries remained unaffected. Cefradine exposure was associated with decreased recoveries of Bifidobacterium spp., Bacteroides spp. and Enterobacteriaceae. These changes were not associated with induction of CDI, as we observed a lack of C. difficile spore germination/proliferation, thus no toxin was detected. This is in contrast to a model exposed to ceftriaxone, where CDI was observed. CONCLUSIONS: These model data suggest that the minimal impact of first-generation cephalosporins, namely cefalexin and cefradine, on the intestinal microbiota results in a low propensity to induce CDI.

An Open-Label, Randomized, 2-Way, Crossover Bioequivalence Study of Cefradine Capsules in Healthy Chinese Volunteers.

The purpose of this study was to evaluate whether test cefradine capsules and reference cefradine capsules were bioequivalent in healthy Chinese volunteers. An open-label, randomized, biperiodic, crossover design was used. In each of the 2 study periods (separated by a 1-week washout period), 250-mg single doses of either the test or reference cefradine capsule were administered to study participants under fasted and fed conditions. Blood samples were collected at intervals from predose to 8 hours afterward. In the fasting study, the 90% confidence intervals (90%CI) of the Cmax , AUC0-8h , and AUC0-∞ for the test and reference preparations were 93.7%-112.2%, 94.6%-100.8%, and 94.7%-100.9%, respectively. In the fed study, the 90%CI of the Cmax , AUC0-8h , and AUC0-∞ for the test and reference preparations was 81.0%-99.1%, 100.5%-106.3%, and 100.5%-105.9%, respectively. The results showed that the test cefradine capsules and the reference formulation are bioequivalent under both fasting and fed conditions.

[Non-Necrotizing Acute Dermo-Hypodermal Infections: Erysipela and Infectious Cellulitis]. / Dermo-Hipodermites Bacterianas Agudas Não Necrotizantes: Erisipela e Celulite Infeciosa.

Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A ß-haemolytic streptococcus. The lower limbs are affected in more than 80% of cases and the risk factors are disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical and in a typical setting we observe an acute inflammatory plaque with fever, lymphangitis, adenopathy and leucocytosis. Bacteriology is usually not helpful because of low sensitivity or delayed positivity. In case of atypical presentations, erysipela must be distinguished from necrotizing fasciitis and acute vein thrombosis. Flucloxacillin and cefradine remain the first line of treatment. Recurrence is the main complication, so correct treatment of the risk factors is crucial.

As dermo-hipodermites bacterianas agudas não necrotizantes são processos infeciosos que incluem a erisipela e a celulite infeciosa, e são geralmente causadas por estreptococos ß­hemolíticos do grupo A. Em mais de 80% dos casos situam-se nos membros inferiores e são fatores predisponentes a existência de solução de continuidade na pele, o linfedema crónico e a obesidade. O seu diagnóstico é essencialmente clínico e o quadro típico baseia-se na presença de placa inflamatória associada a febre, linfangite, adenopatia e leucocitose. Os exames bacteriológicos têm baixa sensibilidade ou positividade tardia. Nos casos atípicos é importante o diagnóstico diferencial com a fasceíte necrotizante e a trombose venosa profunda. A flucloxacilina ou a cefradina são os fármacos de primeira linha. A recidiva constitui a complicação mais frequente, sendo fundamental o correto tratamento dos fatores de risco.

Molecular structure and quantum descriptors of cefradine by using vibrational spectroscopy (IR and Raman), NBO, AIM, chemical reactivity and molecular docking.

This study aims to investigate the structural and vibrational features of cefradine (the first-generation cephalosporin antibiotic) based on spectroscopic experiments and theoretical quantum chemical approach. The fundamental structural aspects of cefradine have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, intramolecular hydrogen bonding, and molecular docking analysis. The most stable minimum energy conformer of the title molecule was identified by performing a one-dimensional potential energy surface scan along the rotational bonds at B3LYP/6-311++G (d,p) level of theory. The vibrational features of the molecule and information about the coupled modes were predicted. The chemical reactivity and stability of all the possible conformers of cefradine were estimated based on the HOMO-LUMO energy gap and NBO approach. The overall picture of accumulation of charges on individual atoms of the molecule was predicted by molecular electrostatic potential (MEP) surface map which in turn identifies the nucleophilic and electrophilic region or sites. The quantitative analysis of electrophilicity and nucleophilicity indices was done by Hirshfeld charge analysis and it was found that N8 atom is the most prominent site for nucleophilic attack while C14 atom is feasible for electrophilic attack. QTAIM study has also been performed to investigate the nature and strength of hydrogen bonding interactions. Besides, molecular docking studies were performed to examine the active binding residues of the target.

Degradation of cefradine in alga-containing water environment: a mechanism and kinetic study.

Large quantities of antibiotics are manufactured, used, and eventually discharged into alga-containing water environment as prototypes, by-products, or transformation products. Different activities of Chlamydomonas reinhardtii toward cefradine (CFD) were studied, and the results indicated that CFD is resistant (removal rate of 5.45-14.72%) in simulated natural water environment. Cefradine was mainly removed by hydrolysis, adsorption, desorption, photodecarboxylation, and photoisomerization. The effects of C. reinhardtii density, initial solution pH, and different light sources on CFD removal efficiency were investigated. The optimum conditions occurred at a density of algae 10 × 104 cells/mL, a solution pH of 9.0, and the ultraviolet (UV) light. Additionally, the removal kinetics under 16 different conditions was explored. The results showed that the removal of CFD fits well with a pseudo-first-order kinetic, and the half-life times are from 0.8 to 261.6 days. This study summarizes the CFD removal mechanisms in alga-containing water environment, highlights the important role played by light irradiation in eliminating CFD, and obtains the important kinetic data on CFD removal.

Controlled release of cephradine by biopolymers based target specific crosslinked hydrogels.

The novel silane crosslinked (TEOS) hydrogels based on eco-friendly biodegradable chitosan/guargum were prepared by blending with PEG to develop pH sensitive hydrogels (CGP) and achieved its hydrophilicity and target specificity for controlled release of drug. The crosslinker amount was varied to analyze its effect on the hydrogel properties and were characterized using FTIR, SEM, TGA, swelling studies (water, buffer and ionic solution) and in-vitro release of cephradine (CED). FTIR confirmed the presence of characteristic peaks and crosslinking between the components while SEM images showed the formation of clear micro- and macro-pores. The swelling behavior in water showed that compared to the controlled hydrogel, the crosslinked hydrogels revealed more swelling but a decrease in swelling with further increase in the amount of crosslinker was observed. The hydrogels showed low swelling at basic and neutral pH while maximum swelling was observed at acidic pH. This pH response made these hydrogels an ideal candidate for injectable controlled release. The CED was loaded on hydrogels and its release mechanism was studied in PBS, SGF and SIF which revealed that out of all hydrogels (CGP100, CGP150, CGP200 and CGP250), CGP100 has shown CED release of 85% in 130 min in PBS and 82.4% in SIF.

A comparative study of different aspects in manipulating ratio spectra used for the analysis of cefradine in the presence of its alkaline degradation product.

Six stability-indicating UV-spectrophotometric methods manipulating ratio spectra were utilized for the analysis of cefradine in presence of its alkaline degradate. These methods are different forms of transformations; ratio difference, mean centering, derivative ratio using numerical differentiation, derivative ratio using Savitsky-Golay filter, continuous wavelet transform and derivative continuous wavelet transform. Water was used as a solvent and the linearity ranges were 6-26 µg/mL. Determination of accuracy and precision for the suggested procedures were executed. Assessment of specificity was run through analyzing laboratory prepared mixtures containing cefradine and its alkaline degradate. The suggested methods were useful for cefradine estimation in tablets. Statistically, the outputs obtained from the recommended and published methods reveal no significant differences.

Study on the interaction mechanism between cefradine and Chlamydomonas reinhardtii in water solutions under dark condition.

Our research investigated the hormesis effect of cefradine on the specific growth rates (µ) of single-celled algae (Chlamydomonas reinhardtii) from aqueous solutions. We found the specific growth rate of C. reinhardtii slightly increased with cefradine concentrations within the range 0.5-10 mg/L. Effects of algae density, initial solution pH, and temperature on the adsorption batch assays were investigated. The optimum conditions for cefradine adsorption occurred at a density of 5 × 106 algae cells/mL, a solution pH of 7.0, and a temperature of 25.0 °C. A Box-Behnken design was employed to evaluate correlations between influential factors and cefradine adsorption. The results showed a significant interaction between algae density and temperature. The maximum removal rate could reach 50.13% under the optimal conditions. Additionally, the adsorption mechanisms were explored through Langmuir and Freundlich isotherm equations, adsorption kinetics, and thermodynamics. The results suggested that the adsorption process was monolayer, spontaneous, and endothermic with an increase in randomness at the algae-solution interface, which followed a pseudo-second-order model. All the data indicated that the alga performed a better removal capacity in the antibiotic-containing wastewater treatment process. This study lays the groundwork for a better understanding of the interaction mechanism between cefradine and Chlamydomonas reinhardtii in water solutions under dark condition.

Comprehensive assessment of three typical antibiotics on cyanobacteria (Microcystis aeruginosa): The impact and recovery capability.

This innovative study provided a comprehensive evaluation of the effects of three typical antibiotics exposures (cefradine, norfloxacin and amoxicillin) on Microcystis aeruginosa in two periods (exposure and post-exposure) at a new perspective. The results indicated that the irreversible growth inhibition of M. aeruginosa attributed to the norfloxacin in the exposure and the re-exposure stages. In contrast, although the algal cell size recovered to the control level after the exposure of 20 mg/L of cefradine, the significant stimulation on glutathione (GSH) still persisted even if the contaminants were removed. On the other hand, amoxicillin inhibited the activities of superoxide dismutase (SOD), GSH contents and the algal cell size in the exposure period while malonaldehyde (MDA) contents increased significantly in two periods.

Detection of the iron complexes with hydrolysis products of cephalexin and cefradine upon high-performance liquid chromatography/electrospray ionization mass spectrometry analysis.

RATIONALE: Cephalosporins (e.g. cephalexin, cefradine) are a major group of widely used ß-lactam antibiotics. Hydrolysis of the ß-lactam ring is an important reaction (often undesired) which leads to deactivation of ß-lactams. To the best of our knowledge there is no electrospray ionization mass spectrometry (ESI-MS) data reported concerning the products of hydrolysis of cephalosporins. METHODS: The hydrolysis of cephalexin and cefradine was performed in aqueous NaOH solutions. After the process the solutions were analyzed by high-performance liquid chromatography (HPLC)/ESI-MS. The elemental compositions of the ions discussed were confirmed by the accurate mass measurements on a quadrupole time-of-flight (QTOF) mass spectrometer. RESULTS: Unexpectedly, complexes between the hydrolysis products of cephalexin and cefradine (CFLh and CFRh ) and iron cation were detected upon HPLC/ESI-MS analysis, namely the ions [(CFLh -H)2 +Fe]+ and [(CFRh -H)2 +Fe]+ , although iron was not added to the analyzed solutions or to the mobile phase. These ions were found to be very stable in the gas phase. CONCLUSIONS: The detection of the complexes between the hydrolysis products of cephalosporins and iron may have a positive impact on the sensitivity and specificity of HPLC/ESI-MS analyses of the hydrolysis products of some cephalosporins.