Penicilloic Acid Research Articles

Search for Biomarkers for the LC-ESI-QqQ Determination of Phenoxymethylpenicillin Treatment in Raw or Cooked Chicken Meat Samples.

The high standards required for food safety make it necessary to trace unambiguously raw or cooked food products coming from medicated animals. Nevertheless, considering the lability of β-lactams and their degradation, the detection of the presence of antibiotics in meat either raw or submitted to a cooking process is not easily affordable. To achieve this goal, an evaluation of the effect of common domestic cooking procedures, such as boiling and grilling, on the fate of phenoxymethylpenicillin (PENV) residues was performed. Finally, in this work, the penilloic acid from PENV (MET02) and the corresponding penicilloic acid (PENV-HYDRO) are suggested as biomarkers. These compounds present the highest relative abundances 5 days after the treatment was stopped (5PT) and show enough thermal stability to be considered suitable biomarker candidates for the pharmacological treatment instead of the parent compound. Nevertheless, the peaks corresponding to MET02 are significantly more intense than those for PENV-HYDRO, which makes preferential the use of MET02 to perform the control of samples.

Synthesis of potential impurities of cloxacillin sodium drug substance

AbstractThe present work describes the synthesis and characterization of six related compounds of cloxacillin sodium (1) viz penicilloic acid of cloxacillin (2), (3‐(2‐chlorophenyl)‐5‐methylisoxazole‐4‐carbonyl) glycine (Glycine analogue of cloxacillin) (3), CMICAA adduct of cloxacillin (4), (4S)‐2‐(carboxy(3‐(2‐chlorophenyl)‐5‐methylisoxazole‐4‐carboxamido) methyl)‐3‐(2‐ethylhexanoyl)‐5,5‐dimethylthiazolidine‐4‐carboxylic acid (N‐2‐ethylhexanoyl penicilloic acid of cloxacillin) (5), N‐Acetylated penicilloic acid of cloxacillin (6), and Cloxacillin Penicillamide (7). These related compounds are very essential in the process development of cloxacillin sodium and are used as reference standards to determine the quality of the drug substance.

Molecular docking of human serum albumin with penicillin G determinants

Background: Human serum albumin (HSA) is the main pharmacokinetic effector of many medications, including penicillin G and its metabolites. An urgent problem of practical medicine is immediate hypersensitivity reactions caused by penicillin toxicity (about 8 % compared to other medications), accompanied by skin pathology, anaphylaxis, and fatality. Objectives: The aim of this study is to describe the structures of penicillin G determinants-HSA complexes and to identify favorable binding sites and the amino acid residues involved in the interaction. Material and Methods: The crystal structure of HSA (ID: 1AO6 from Protein Data Bank) (www.rcsb.org) was chosen as a docking target. Molecular docking methods (AutoDock Tools 1.5.7, AutoDock Vina 1.1.2) were used to gain insight into the interaction of HSA with the major (benzyl penicilloyl G, penicillanic acid) and minor (penicillamine, penicilloic acid, penilloic acid) determinants of penicillin G. Visualization of docking results was implemented in PyMol 2.5. The Protein Plus server (https://proteins.plus) was used to evaluate potential binding pockets. The PLIP tool (https://plip-tool.biotec.tu-dresden.de) was used to identify non-covalent interactions between HSA and its ligands. Results: The molecular docking data indicate that the major determinants of penicillin G are involved in the formation of hydrogen bonds with such HSA residues as Trp214, Arg218, His242, and Asn295; for the minor determinants — Asp108, His146, Tyr148, Ser193, Arg197, Gln204. Both types of determinants are located in the hydrophobic cavity of subdomains IIA and IB. Hydrophobic interactions are present mainly between penicillin G determinants and amino acid residues of subdomain IIIA, such as Ala350, Asp451, Tyr452, and Gln459. Conclusion: The study of penicillin G determinants-HSA complexes is important in the pathogenesis of antibiotic allergy. Identification of specific binding sites can be useful for the development and synthesis of new immunogenic antigens (complexes of major and minor determinants of penicillin G with HSA) that can stimulate the immune system and produce specific antibodies to prevent allergic reactions.

Predicting bioactivity of antibiotic metabolites by molecular docking and dynamics

Antibiotics enter the environment through waste streams, where they can exert selective pressure for antimicrobial resistance in bacteria. However, many antibiotics are excreted as partly metabolized forms, or can be subject to partial breakdown in wastewater treatment, soil, or through natural processes in the environment. If a metabolite is bioactive, even at sub-lethal levels, and also stable in the environment, then it could provide selection pressure for resistance. (5S)-penicilloic acid of piperacillin has previously been found complexed to the binding pocket of penicillin binding protein 3 (PBP3) of Pseudomonas aeruginosa. Here, we predicted the affinities of all potentially relevant antibiotic metabolites of ten different penicillins to that target protein, using molecular docking and molecular dynamics simulations. Docking predicts that, in addition to penicilloic acid, pseudopenicillin derivatives of these penicillins, as well as 6-aminopenicillanic acid (6APA), could also bind to this target. MD simulations further confirmed that (5R)-pseudopenicillin and 6APA bind the target protein, in addition to (5S)-penicilloic acid. Thus, it is possible that these metabolites are bioactive, and, if stable in the environment, could be contaminants selective for antibiotic resistance. This could have considerable significance for environmental surveillance for antibiotics as a means to reduce antimicrobial resistance, because targeted mass spectrometry could be required for relevant metabolites as well as the native antibiotics.

Interactions of hydrolyzed β-lactams with the L1 metallo-β-lactamase: Crystallography supports stereoselective binding of cephem/carbapenem products

L1 is a dizinc subclass B3 metallo-β-lactamase (MBL) that hydrolyzes most β-lactam antibiotics and is a key resistance determinant in the Gram-negative pathogen Stenotrophomonas maltophilia, an important cause of nosocomial infections in immunocompromised patients. L1 is not usefully inhibited by MBL inhibitors in clinical trials, underlying the need for further studies on L1 structure and mechanism. We describe kinetic studies and crystal structures of L1 in complex with hydrolyzed β-lactams from the penam (mecillinam), cephem (cefoxitin/cefmetazole), and carbapenem (tebipenem, doripenem, and panipenem) classes. Despite differences in their structures, all the β-lactam-derived products hydrogen bond to Tyr33, Ser221, and Ser225 and are stabilized by interactions with a conserved hydrophobic pocket. The carbapenem products were modeled as Δ1-imines, with (2S)-stereochemistry. Their binding mode is determined by the presence of a 1β-methyl substituent: the Zn-bridging hydroxide either interacts with the C-6 hydroxyethyl group (1β-hydrogen-containing carbapenems) or is displaced by the C-6 carboxylate (1β-methyl-containing carbapenems). Unexpectedly, the mecillinam product is a rearranged N-formyl amide rather than penicilloic acid, with the N-formyl oxygen interacting with the Zn-bridging hydroxide. NMR studies imply mecillinam rearrangement can occur nonenzymatically in solution. Cephem-derived imine products are bound with (3R)-stereochemistry and retain their 3' leaving groups, likely representing stable endpoints, rather than intermediates, in MBL-catalyzed hydrolysis. Our structures show preferential complex formation by carbapenem- and cephem-derived species protonated on the equivalent (β) faces and so identify interactions that stabilize diverse hydrolyzed antibiotics. These results may be exploited in developing antibiotics, and β-lactamase inhibitors, that form long-lasting complexes with dizinc MBLs.

Synthesis and characterization of degradation impurities of Flucloxacillin and Dicloxacillin

AbstractA series of degradation impurities of Flucloxacillin and Dicloxacillin were synthesized. The formation and a facile synthesis of each impurity were presented in detail, namely penicilloic acids of Dicloxacillin (3) (Ph.Eur. Impurity‐A), Dicloxacillin glycine analog (4), Dicloxacillin penilloic acids (5) (Ph.Eur. Impurity‐B), Dicloxacillin Pencillamide (6), N‐Acetylated penicilloic acid of Dicloxacillin (7), DCMICAA adduct of Dicloxacillin penicilloic acid (8), Flucloxacillin glycine analog (Ph.Eur. Impurity‐F) (9), penicilloic acids of Flucloxacillin (10), penilloic acids of Flucloxacillin (11), CFMICAA adduct of Flucloxacillin penicilloic acid (Flucloxacillin Ph.Eur. Impurity‐H) (12), Flucloxacillin Penicillamide (Flucloxacillin Ph.Eur. Impurity‐E) (13), and N‐Acetylated penicilloic acid of Flucloxacillin (14). These impurities are extensively characterized by various analytical techniques.

Increased coverage and high confidence in suspect screening of emerging contaminants in global environmental samples

Suspect screening using liquid chromatography with high resolution mass spectrometry provides an opportunity for expanding the detection coverage of emerging contaminants in the environment. Screening workflows may suffer from high frequency of false positives or insufficient confidence in the identification of compounds; however, stringent criteria could lead to high false negatives. A workflow must have a balanced criteria, both selective and sensitive, to be able to identify real features without missing low abundant features traceable to analytes of interest. A highly selective (87%) and sensitive (97%) workflow was developed by characterizing the occurrence of contaminants in wastewater and surface water from Hong Kong, India, Philippines, Sweden, Switzerland, and the U.S. Sixty-eight contaminants were identified and confirmed with reference standards, including pharmaceuticals, pesticides, and industrial chemicals. The antimicrobials metronidazole, clindamycin, linezolid, and rifaximin were detected. Notably, antifungal compounds were detected in samples from six countries, with levels up to 1380 ng/L. Amoxicillin transformation products, penilloic acid (285–8047 ng/L) and penicilloic acid (107 ng/L), were confirmed for the first time with reference standards in wastewater samples from India, Sweden, and U.S. This workflow provides an efficient approach to broad-scale identification of emerging contaminants using publicly-available databases for suspect screening and prioritization.

A two-dimensional photonic crystal hydrogel biosensor for colorimetric detection of penicillin G and penicillinase inhibitors.

A simple penicillinase functionalized two-dimensional photonic crystal hydrogel (2DPPCH) biosensor was developed for colorimetric detection of penicillin G and penicillinase inhibitors. The penicillinase can specifically recognize penicillin G and catalyze it to produce penicilloic acid, which decreases the pH of the hydrogel microenvironment and shrinks the pH-sensitive hydrogel. The particle spacing decrease of the 2D photonic crystal array induced by the hydrogel shrinkage further causes a blue-shift in the diffraction wavelength. While the hydrolysis reaction is repressed upon treatment with clavulanate potassium (a kind of penicillinase inhibitor), no significant change in the diffraction wavelength is found. The detection of targets can be achieved by measuring the Debye diffraction ring diameter or observing the structural color change in the visible region. The lowest detectable concentrations for penicillin G and clavulanate potassium are 1 μM and 0.1 μM, respectively. Moreover, the 2DPPCH is proved to exhibit high selectivity and an excellent regeneration property, and it shows satisfactory performance for penicillin G analysis in real water samples.

Fluorescent Mesoporous Nanoparticles for β-Lactamase Screening Assays.

We present a sensitive and rapid screening method for the determination of β‐lactamase activity of antibiotic‐resistant bacteria, by designing a pH‐sensitive fluorescent dye‐doped mesoporous silica nanoparticle encapsulated with penicillin G as a substrate. When penicillin G was hydrolysed by β‐lactamase and converted into penicilloic acid, the acidic environment resulted in fluorescence quenching of the dye. The dye‐doped mesoporous nanoparticles not only enhanced the β‐lactamase‐catalyzed reaction rate but also stablized the substrate, penicillin G, which degrades into penicilloic acid in a water solution without β‐lactamase. Twentyfive clinical bacterial samples were tested and the antibiotic resistant and susceptible strains were identified. The proposed method may detect the presence of β ‐lactamases of clinically relevant samples in less than 1 hour. Moreover, the detection limit of β‐lactamase activity was as low as 7.8×10−4 U/mL, which was determined within two hours.

Multi-class analysis of 46 antimicrobial drug residues in pond water using UHPLC-Orbitrap-HRMS and application to freshwater ponds in Flanders, Belgium

Increasing anthropogenic pressure and agricultural pollution raises concerns regarding antimicrobial resistance and biodiversity loss in aquatic environments. In order to protect and restore water resources and biodiversity, antimicrobial drug residues should be monitored in all aquatic environments including pond water. Consequently, the objective of this research was to develop and validate a novel multi-residue method for the simultaneous quantification of 46 targeted human and veterinary antimicrobial drugs in pond water. A suitable extraction method based on solid-phase extraction (SPE) was developed, assisted by a fractional factorial design. A broad polarity range of compounds was covered (log P from −4.05 to 4.38), including major representatives of the following classes: sulfonamides, tetracyclines, quinolones, macrolides, lincosamides, nitrofurans, penicillins, cephalosporins, diaminopyrimidines, pleuromutilins and phenicols. All analytes were separated using ultra-high performance liquid chromatography (UHPLC) and detected in full-scan by Orbitrap high resolution mass spectrometry (Orbitrap-HRMS). Good linearity was obtained for all compounds with R2 ≥ 0.993 and goodness-of-fit coefficient (g) ≤ 11.56%. Method detection limits ranged from 10 to 50 ng L−1 and method quantification limits were 50 ng L−1 for all compounds. Acceptable values were obtained for within-day and between-day apparent recoveries (i.e. between 50 and 120%), precision (< 30% and < 45%) and measurement uncertainty (< 50%). Targeted analysis of 18 freshwater ponds throughout Flanders was performed to demonstrate the applicability of the newly developed UHPLC-HRMS method. Overall, 20 antimicrobial drugs were detected with highest concentrations observed for tetracyclines and their transformation products ranging between 51 and 248 ng L−1. Finally, suspect screening was performed suggesting the presence of 14 additional pharmaceuticals including 3 antimicrobial degradation products (e.g. apo-oxytetracycline, amoxicillin penicilloic acid and penilloic acid) and 11 pesticides.

Mechanistic and ecotoxicological studies of amoxicillin removal through anaerobic degradation systems

Many studies have been conducted on the evaluation and monitoring of micropollutants and by-products in wastewater treatment plants. Considering the increase in the production and consumption of emerging contaminants, such as drugs, personal care products, and plasticisers, it is necessary to conduct studies that support the elaboration of laws and regulations that promote the environmentally sustainable use of sludge and effluents. In this work, the biological degradation of amoxicillin was studied under two anaerobic conditions: i) using a 6L reactor operated under semi-continuous flow; and ii) a batch system with 100mL sealed glass syringes. According to the statistical analysis, amoxicillin was completely removed from the systems, but biogas production inhibition was observed (p<0.05). Liquid chromatography-high-resolution mass spectrometry analysis identified amoxicillin penicilloic acid, amoxilloic acid, amoxicillin diketopiperazine and phenol hydroxypyrazine as by-products under anaerobic conditions. Ecotoxicity tests on effluent treated under the batch conditions showed that the addition of higher amounts of amoxicillin inhibited the target species Aliivibrio fischeri and Raphidocelis subcaptata, causing functional decreases of 28.5% and 22.2% when the antibiotic concentration was 2500μgL-1. A. fischeri was the most sensitive organism to effluent treated under semi-continuous flow conditions; a continuous reduction in bioluminescence of up to 88.8% was observed after 39 days of feeding, which was associated with by-products accumulation due to unbalanced conditions during anaerobic digestion. Changes in the physico-chemical characteristics of the effluent caused the accumulation and removal of AMX-DKP IV and modified the toxicity to Lactuca sativa and R. subcapitata.

3D printed chitosan scaffolds: A new TiO2 support for the photocatalytic degradation of amoxicillin in water

TiO2-supported chitosan scaffolds (TiO2/CS) are here proposed as promising material for wastewater treatment, in particular for the removal of pharmaceutical compounds. TiO2/CS are tested for the amoxicillin photodegradation under UV/Vis irradiation. Amoxicillin (AMX) is an antibiotic of the beta-lactam family. Due to the release of antibiotics in wastewater and their persistence in the environment, harmful effects can develop on the aquatic and terrestrial organisms.TiO2 chitosan scaffolds with photocatalytic activity for wastewater remediation have been prepared by 3D printing using commercial P25-TiO2. The formulation for the 3D printer was prepared by dispersion of chitosan and TiO2 in powder form at the concentration 6% w/v and 1% w/v, respectively. The TiO2 particles (crystalline anatase and rutile phases) embedded in the chitosan have a size of about 20 nm, like in the starting material, as verified by X-ray diffraction and Raman spectroscopy and are homogeneously distributed in the scaffold, also after repeated photocatalytic tests, as revealed by SEM-EDS.The mechanical properties of the 3D structures are suitable for the targeted application as they can be easily handled without breakage.The AMX photodegradation efficiency under light irradiation by TiO2/CS made with scaffolds of different thicknesses (3, 5, 15 layers), was assessed in water by means of UV–Vis absorption and HPLC/UV measurements, at two different AMX:TiO2 molar ratios: 1/100 and 1/10. The 3D printed TiO2/CS system, even after repeated cycles, shows a high photodegradation efficiency, compared to the direct AMX photolysis. A zero-order kinetics for TiO2 supported photodegradation was found, whereas a pseudo-first order was observed for water dispersed TiO2.Mass spectrometry analysis revealed the presence of AMX degradates such as penilloic and penicilloic acids and diketopiperazine.The proposed 3D printed chitosan scaffolds may be used as reusable substrate for the TiO2 photocatalytic degradation of antibiotic pollutants in wastewater.

Novel insights into the chemistry of an old medicine: A general degradative pathway for penicillins from a piperacillin/tazobactam stability study

Piperacillin is a broad spectrum beta-lactam antibiotic used in combination with tazobactam for hospital-related bacterial infections. The reconstituted solutions must respect the sub-visible and visible particles specifications. It was claimed that the reformulation containing EDTA/sodium citrate was able to control the formation of an insoluble impurity responsible for the formation of particulate matter observed using Ringer Lactate as diluent. The nature of the impurities formed during the degradative process of piperacillin/tazobactam combination has been herein investigated, by exploring the effect of added excipients and pH variations. The exact structure of the isolated dimeric impurity, the penicilloic acid-piperacillin dimer, was determined through complete characterization, allowing to propose a novel degradative general pathway for beta-lactam antibiotics. The presence of EDTA resulted unnecessary to contain the formation of the insoluble impurity, since the use of sodium citrate alone allowed to avoid this drawback. Finally, the proposed mechanism was successfully applied to the design of a novel, easy and high purity procedure for the synthesis of the acetylated penicilloic acid, known related substance of piperacillin.

Ampicillin permeation across OmpF, the major outer-membrane channel in Escherichia coli

The outer cell wall of the Gram-negative bacteria is a crucial barrier for antibiotics to reach their target. Here, we show that the chemical stability of the widely used antibiotic ampicillin is a major factor in the permeation across OmpF to reach the target in the periplasm. Using planar lipid bilayers we investigated the interactions and permeation of OmpF with ampicillin, its basic pH-induced primary degradation product (penicilloic acid), and the chemically more stable benzylpenicillin. We found that the solute-induced ion current fluctuation is 10 times higher with penicilloic acid than with ampicillin. Furthermore, we also found that ampicillin can easily permeate through OmpF, at an ampicillin gradient of 10 μm and a conductance of Gamp ≅ 3.8 fS, with a flux rate of roughly 237 molecules/s of ampicillin at Vm = 10 mV. The structurally related benzylpenicillin yields a lower conductance of Gamp ≅ 2 fS, corresponding to a flux rate of ≈120 molecules/s. In contrast, the similar sized penicilloic acid was nearly unable to permeate through OmpF. MD calculations show that, besides their charge difference, the main differences between ampicillin and penicilloic acid are the shape of the molecules, and the strength and direction of the dipole vector. Our results show that OmpF can impose selective permeation on similar sized molecules based on their structure and their dipolar properties.

Degradation kinetics and mechanism of penicillin G in aqueous matrices by ionizing radiation

The gamma radiation induced-degradation of a β-lactam antibiotic, penicillin G was investigated in aqueous solution. Special attention was paid to the effects of the organic substances such as peptone and glucose on penicillin G degradation, which can be found in the wastewater of the factories producing antibiotics. Results showed that gamma radiation was effective to degrade and deactivate penicillin G in pure water. With the initial concentrations of 0.27mM, 1.34mM and 2.68mM, a complete removal of penicillin G could be achieved at the adsorbed doses of 2.5kGy, 10kGy and 20kGy, respectively. Penicilloic acid from the β-lactam ring cleavage and a series of fragment compounds such as thiazolidine and penicillic acid were identified during gamma irradiation-induced degradation of penicillin G. Addition of Fe2+ was efficient to enhance the mineralization. The TOC removal efficiency of penicillin G was 21.7% using gamma irradiation alone at 10kGy, which increased to 56.4% with 1.0mM Fe2+ addition. The gamma radiation-induced degradation of penicillin G was inhibited in the presence of peptone and glucose and the inhibitive effect increased with increasing their concentrations. The rate constant, k of the pseudo first-order kinetics decreased by 74% and 64% in the presence of 1.0g/L of peptone and glucose, respectively, and by 96% and 89% in the presence of 10g/L of peptone and glucose, respectively. The ratio of k/k0 was increased by 1.3 times with H2O2 addition and by 3 times with Fe2+ addition, in the presence of 10g/L of glucose. Adding Fe2+ was effective to improve the ionizing radiation induced degradation of penicillin G antibiotic in the glucose-containing wastewater.

Variations in the fate and risk analysis of amoxicillin and its degradation products during pig manure aerobic composting

In this study, 100 mg/kg of amoxicillin (AMX) was added to pig manure during aerobic composting using a laboratory-scale reactor system, for better understanding the degradation of AMX and its potential risks. Qualitative and quantitative analysis of AMX and its main degradation products (DPs) were then conducted using solid phase extraction combined with high performance liquid chromatography-tandem mass spectrometry. Additionally, hydrolysis testing was performed to monitor DPs produced from AMX degradation under various controlled conditions. The results showed that AMX was unstable in compost and rapidly degraded into AMX penicilloic acid, AMX penilloic acid and AMX diketopiperazine, which all eventually degraded, leaving a structurally simple and stable end product, 3-(4-hydroxyphenyl) pyrazin-2-ol, which appeared to be nonallergenic and less toxic than DPs generated earlier in the composting process. Besides, AMX was more unstable and more apt to generate multiple DPs in alkaline conditions than in acidic or neutral conditions or in ultrapure water, while pH exerted a larger effect on AMX degradation than did divalent metal ions (Cu2+ and Zn2+). This study provides technical and methodological support to better achieve AMX residual treatment and to evaluate the safety of AMX DPs produced in huge quantities in compost in China.

Colorimetric assay for β-lactamase activity using cocktail of penicillin and 4-(2-pyridylazo)resorcinol (PAR)–2Hg2+ complex

A colorimetric assay method for measuring β-lactamase activity was developed using a cocktail of penicillin and 4-(2-pyridylazo)resorcinol (PAR)–2Hg2+ complex. The penicilloic acid that hydrolyzed form of penicillin by β-lactamase chelates with mercury ion of PAR–2Hg2+ complex effectively, conversion of PAR–2Hg2+ complexes to free PAR induced the color change from red to yellow. Exact measurement of β-lactamase activity can be performed by the spectrophotometric method, and the facile monitoring of β-lactamase activity was possible in real time. Also, this colorimetric method was applied to determine the Michaelis constant (Km) of β-lactamase and the IC50 of clavulanic acid. Given the facts that its simplicity and high assay speed, this method may be extended to high-throughput screening of β-lactamase inhibitors.

Label-Free Photonic Crystal-Based β-Lactamase Biosensor for β-Lactam Antibiotic and β-Lactamase Inhibitor

A simple, label-free, and visual photonic crystal-based β-lactamase biosensor was developed for β-lactam antibiotic and β-lactamase inhibitor in which the penicillinase (a β-lactamase) was immobilized on the pH-sensitive colloidal crystal hydrogel (CCH) film to form penicillinase colloidal crystal hydrogel (PCCH) biosensing film. The hydrolysis of penicillin G (a β-lactam antibiotic) can be catalyzed by penicillinase to produce penicilloic acid, leading to a pH decrease in the microenvironment of PCCH film, which causes the shrink of pH-sensitive CCH film and triggers a blue-shift of the diffraction wavelength. Upon the addition of β-lactamase inhibitor, the hydrolysis reaction is suppressed and no clear blue-shift is observed. The concentrations of β-lactam antibiotic and β-lactamase inhibitor can be sensitively evaluated by measuring the diffraction shifts. The minimum detectable concentrations for penicillin G and clavulanate potassium (a β-lactamase inhibitor) can reach 1 and 0.1 μM, respectively. Furthermore, the proposed method is highly reversible and selective, and it allows determination of penicillin G in fish pond water samples.

Removal and degradation of β-lactam antibiotics in water using didodecyldimethylammonium bromide-modified montmorillonite organoclay

β-Lactam antibiotics including penicillin G, nafcillin, cefazolin, cefotaxime, and oxacilline in water were rapidly removed and degraded by using didodecyldimethylammonium bromide (DDAB)-montmorillonite (MT) organoclay. Removal of antibiotics increased with increasing the amount of organoclay added and the amount of DDAB sorbed on MT. Extents of organoclay sorption of antibiotics were represented by the binding constants to DDAB molecules and correlated to the aqueous-octanol distribution coefficients. The degradation rate of β-lactam antibiotics was found to significantly increase by the organoclay sorption. Even under the mild conditions (25°C and pH 7), penicillin G (m/z=335) nearly completely (>98%) degraded into penicilloic acid (m/z=353) missing β-lactam ring within 2h. The first-order reaction rate of the primary degradation increased with increasing in temperature. The activation energy estimated from the Arrhenius plot was 49kJmol−1 and lower than the value (83.5kJmol−1) in water, strongly suggesting catalytic activity of DDAB-MT organoclay. The applicability to wastewater treatment was demonstrated by using secondary effluents of municipal sewage treatment plants and synthesized hospital wastewaters.

Laboratory Investigation of Antibiotic Interactions with Fe2O3 Nanoparticles in Water

AbstractThe movement and degradation of drugs in soil and water environments are related to surface interactions with oxide nanoparticles. These nanoparticles could be stationary substrates or suspended in aqueous solution. In this study, different pH solutions of the common antibiotic ampicillin (AMP) were mixed with ≤50-nm Fe2O3 (maghemite) particles. Both sorption and breakdown of AMP were observed. For initial drug concentrations from ∼3 μM to 2.9 mM, the overall AMP removal from solution can be described by linear isotherms with removal coefficients (Kr) of 394 (±43) L kg−1 at pH 2, 551 (±37) L kg−1 at pH 6, and 256 (±37) L kg−1 at pH 8. At pH 4, AMP removal can be described by a Freundlich isotherm of log Kf=3.27 (±0.19) and n=0.57 (±0.15). AMP solutions were separated from maghemite nanoparticles after mixing and analyzed by liquid chromatography/mass spectroscopy (LC/MS) techniques, resulting in the detection of penicilloic and penilloic acid breakdown products.