Published in J. Environ. Qual. 33:257-264 (2004).
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677 S. Segoe Rd., Madison, WI 53711 USA
TECHNICAL REPORTS
Organic Compounds in the Environment
Adsorption and Clay-Catalyzed Degradation of Erythromycin A on Homoionic Clays
Yong-Hak Kim,
Thomas M. Heinze,
Seong-Jae Kim and
Carl E. Cerniglia*
Div. of Chemistry, National Center for Toxicological Research, U.S. Food and Drug Admin., Jefferson, AR 72079
* Corresponding author (ccerniglia{at}nctr.fda.gov).
Received for publication April 8, 2003.
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ABSTRACT
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Erythromycin has been widely used in food-producing animals and in humans, and is frequently detected as an organic pollutant in U.S. streams. In batch experiments with homoionic clays, the Freundlich isotherms were determined at 10 and 25°C. The adsorption of erythromycin A was strongly influenced by clay type, exchanged cations, the pH of the bulk solutions, and the acidity of clay surfaces. The formation of clay–erythromycin A complexes was thermodynamically favorable except for K+– and Fe3+–exchanged montmorillonites, since the reactions were exothermic (
H° > 0) and the systems became stable (S° > 0). Clays catalyzed the erythromycin A degradation by the hydrolysis of the neutral sugar and the multiple dehydrations. The surface acidity of clay surface enhanced the rate of clay-catalyzed degradation of erythromycin A. In addition, the Fe3+–exchanged clay minerals seemed to have an electrostatic interaction with the erythromycin A molecule, by which the hydrolysis of the neutral sugar was influenced.
Abbreviations: HPLC, high-performance liquid chromatography
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INTRODUCTION
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ERYTHROMYCIN A IS WIDELY used for the treatment and prevention of infectious bacterial diseases in humans, livestock, and poultry (Pothuluri et al., 1998), and is also used under Investigative New Animal Drug (INAD) permits in the USA to treat some fish diseases in food fish. Treatment of food-producing animals with antimicrobial agents may increase public health risks by transfer of antibiotic-resistant zoonotic pathogens or the resistance genes from animals to humans (Piddock, 1996; Davies, 1997; Tollefson et al., 1998; World Health Organization, 1998). Erythromycin A is the antibiotic most frequently detected in U.S. streams (Kolpin et al., 2002). It can reach soils and sediments through manure and other farm wastes (Tolls, 2001). Thus, not only the intestinal microflora of animals exposed to antimicrobial agents, but also the accumulation of antibiotics in soils and sediments can serve as potential reservoirs of antibiotic-resistant microorganisms (Pothuluri et al., 1998; Tollefson et al., 1999; Nawaz et al., 2001).
Erythromycin A is dehydrated to anhydroerythromycin A and erythromycin A enol ether by the acid-catalyzed reactions in aqueous solutions, the rates of which are enhanced by the decrease of the pH (Atkins et al., 1986; Cachet et al., 1989). In aqueous solutions, the pH is the critical factor determining the pseudo-first-order reaction rates of the acid- and base-catalyzed erythromycin A degradation to form anhydroerythromycin A and pseudoerythromycin A enol ether as the major products (Y.-H. Kim, T.M. Heinze, and C.E. Cerniglia, unpublished data, 2003). Since erythromycin A molecules are weakly basic (pKa = 8.36), the adsorption of the protonated species on clays may be one of the most important factors influencing the biological activity, persistence, and degradation in sediments. However, little is known about the adsorption and degradation processes on the clays. Here we studied the adsorption processes using homoionic clays in batch experiments. The degradation products extracted from erythromycin-rich clays were analyzed with high-performance liquid chromatography (HPLC) with electrochemical detection and mass spectrometry with electrospray ionization to determine the degradation pathways of erythromycin A in aqueous clay suspensions.
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MATERIALS AND METHODS
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Chemicals
Erythromycin hydrate and bromothymol blue were purchased from Sigma (St. Louis, MO). Anhydroerythromycin A and erythromycin A enol ether were prepared by the respective methods of Wiley et al. (1957) and Kurath et al. (1971). Water used was deionized (>18.2 M
) by a Super-Q Plus water purification system (Millipore, Billerica, MA).
Homoionic Clays
Kaolinite and montmorillonite clays were purchased from Fluka Chemical Co. (Milwaukee, WI). The <2-µm fractions were obtained by sedimentation. Each of 10 g (dry wt.) of clays was saturated with Fe3+, Ca2+, K+, or H+ by five repeated treatments with 50 mL of 1 M concentration of metal chloride or hydrogen chloride. The cation-exchanged clays were thoroughly washed with water, and centrifuged for 10 min at 5°C and 8000 rpm. The washing and centrifugation procedures were repeated until chloride ion was no longer detected by the AgNO3 test (Harter and Stotzky, 1971).
The pH of Bulk Solutions and the Acidity of Clay Surfaces
After 1 h of the equilibration of homoionic clay suspensions (solid to solution ratio = 1:100), the particles were removed by the centrifugation at 8000 rpm for 15 min, and the pH values of the supernatants were measured using a Corning pH electrode and a Corning ion analyzer (Corning Glass Works, Elmira, NY) calibrated with the standard buffers at pH 4 and 7 (J.T. Baker, Phillipsburg, NJ). The acidity of the clay surface was titrated with 0.001 M triethylamine during the stirring of 1 g (dry wt.) of a homoionic clay in 100 mL of water. As a pH indicator, 0.5 mg bromothymol blue was added to 100 mL of water, and a blank was titrated with 0.001 M triethylamine to a green color (pKIn = 7.0). The cation exchange capacity was reported as moles of charge per kilogram clay by the following equation:
where T is the titration in milliliters, B is the blank in milliliters, and M is the molarity of triethylamine. Table 1 shows the pH of the bulk solution and the acidity of the clay surface determined at 25°C.
Sample Preparations
Ten milliliters of homoionic clay suspensions containing 2- to 10-mg mL–1 clays were treated in duplicate with five concentration points of erythromycin A (Ci = 100–500 µM) in 45-mL teflon-coated centrifuge tubes. After 24 h of the incubation on a rotary shaker (100 rpm) at 10 or 25°C, the clay suspensions were centrifuged for 15 min at 8000 rpm to determine concentrations of erythromycin A and the degradation products in supernatants and clay particles separately by the HPLC methods. The supernatants were mixed with three volumes of acetonitrile–methanol–0.25 M ammonium acetate (50:10:40 by volume, pH 7.0). The clay particles were extracted twice with 10 mL of 1 M ammonium acetate (pH 7.0) and twice with 10 mL of acetonitrile, and the ammonium acetate–acetonitrile extracts were treated as described below. Test controls, which did not contain clay minerals, were included under the same procedures.
To compare the clay-catalyzed degradation of anhydroerythromycin A, erythromycin A, and erythromycin A enol ether, 20 mg of each compound was added to 100 mL of homoionic clay suspensions (solid to solution ratio = 1:100) to make the final concentration of 200 µg mL–1. The aqueous clay suspensions were incubated for 24 h at 25°C on a rotary shaker (100 rpm). After centrifugation at 8000 rpm for 15 min, supernatants were removed and clay particles were extracted twice with 10 mL of 1 M ammonium acetate (pH 7.0) and twice with 10 mL of acetonitrile. The ammonium acetate and acetonitrile extracts were thoroughly mixed and placed for 1 h at –20°C to separate the acetonitrile phase. The acetonitrile solvent was evaporated under vacuum, and the residues were dissolved in a small quantity of ethyl acetate, and the insoluble particles were removed by filtration through 0.2-µm Teflon membrane. The samples were dried in vacuo using a Speed-Vac system (Savant Instruments, Farmingdale, NY) and stored at –20°C until used.
Analytical Method
Erythromycin A and the degradation products were determined by reversed-phase high-performance liquid chromatography with electrochemical detection (LC/ED). The chromatographic system consisted of an ESA solvent delivery module 581 (ESA Inc., Chelmsford, MA), a guard column packed with C18-µBondapak (Alltech Associate Inc., Deerfield, IL) and a reversed-phase Radial-Pak Resolve Silica cartridge (5-µm particle size, 0.8 x 10 cm; Waters Co., Milford, MA) fixed in a Waters radial compression module. The ESA Coulochem II-500 electrochemical detector was equipped with an ESA Model 5020 guard cell and an ESA Model 5010 dual-electrode cell. Twenty microliters of sample was injected with the ESA Model 545 Autosampler equipped with a Rheodyne 7125 injector and a 20-µL loop. Potentials of the guard cell and the screening and working electrodes in the detector cell were set at +0.90, +0.65, and +0.85 V, respectively. The isocratic mobile phase consisting of acetonitrile, methanol, and 0.25 M ammonium acetate (50:10:40 by volume, respecively; pH 7.0) was pumped at a flow rate of 1 mL min–1. Under these analytical conditions, the compound peaks of erythromycin A and its metabolites were clearly separated, and the standard curves of anhydroerythromycin A, erythromycin A, and erythromycin A enol ether displayed a good linearity with five concentration points of each compound in a given concentration range (r > 0.99 for all), and the respective detection limits (µg mL–1) were 0.34, 0.41, and 0.25 at a signal to noise ratio of three.
The mass analysis was performed with an HP 5989B quadrupole mass spectrometer equipped with an HP 1090L/M HPLC system (Hewlett-Packard, Palo Alto, CA). The mass spectrometer operated in the positive-ion electrospray mode with the capillary exit voltage (CapEx) variable. Full scans were acquired from m/z 50 to 900 at 0.92 scans s–1 for all analyses. Peaks were resolved with a Prodigy ODS3 column (5-µm particle size, 2.0 x 250 mm; Phenomenex, Torrance, CA). The mobile phase was delivered at 0.2 mL min–1 by a linear gradient of acetonitrile to water from 20:80% (v/v) to 80:20% (v/v) in 45 min with constant 3-mM ammonium formate.
Sorption Isotherms
Equilibrium concentrations (Ce, µmol L–1) of erythromycin A in aqueous clay suspensions were determined after 24 h of the equilibration, and the amounts of erythromycin A sorbed on clays (Cs, µmol kg–1) were measured after ammonium acetate–acetonitrile extraction from erythromycin-rich clays. The adsorption isotherms were identified according to the classification of Giles et al. (1960), and the adsorption isotherms were expressed by the Freundlich equation, Cs = KfCnfe, where Kf and nf are the Freundlich sorption coefficients for the capacity and the intensity of clays. The adsorption coefficients were simply determined by the logarithmic form of the Freundlich equation log Cs = log Kf + nf x log Ce.
The changes in the standard Gibbs free energy (G°), enthalpy (H°), and entropy (S°) of adsorption of erythromycin A were evaluated from the following equations:
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where K0 is the thermodynamic equilibrium constant, R is the gas constant, and T is the absolute temperature. From the plot of ln(Cs/Ce) vs. Cs, the K0 was obtained at Cs = 0, as described by Biggar and Cheung (1973).
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RESULTS
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Adsorption and Degradation of Erythromycin A in Homoionic Clay Suspensions
The adsorption coefficients Kf and nf are shown in Table 2. Considering the sorption isotherms, all of the cation-exchanged kaolinites displayed the S curves, which indicated that the adsorption became easier as concentration increases (Fig. 1)
. This implies a tendency of association between the adsorbed molecules to hold them on the surface. In contrast, the nf values of montmorillonites were significantly smaller than those of kaolinites. It may be because of the fact that montmorillonites have much greater activity for the degradation of erythromycin A than do kaolinites. Since smaller molecules of the degradation products could penetrate easily into the inner lattices of montmorillonites, the availability of the sites for the erythromycin A adsorption might remain constant up to saturation.
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Table 2. Freundlich adsorption coefficients (Kf and nf) and the specific activity for degradation of erythromycin A at 10 and 25°C.
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Fig. 1. Adsorption of erythromycin A on homoionic clays with a solid to solution ratio of 1:100 for kaolinite (K) and 1:500 for montmorillonite (M). The adsorption isotherms at 10°C (solid circles) and 25°C (open circles) are fitted to the Freundlich equation with unbroken line curves and broken line curves, respectively.
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The catalytic activity of montmorillonites for the erythromycin A degradation was much greater than that of kaolinites. The catalytic activity was closely related to types of clay minerals and exchanged cations, surface areas of clays, and the acidity of clay surfaces. Being consistent with the cation exchange capacity of homoionic clays given in Table 1, the rates of degradation of erythromycin A increased in the order of K+ < Ca2+ < Fe3+ at 25°C, but at 10°C, K+–exchanged clays showed a greater activity than Ca2+–exchanged clays. Although the cation-exchange capacities of H+–exchanged clays were smaller than Fe3+–exchanged clays, H+–exchanged clays catalyzed the degradation of erythromycin A more rapidly. This might be because of the fact that hydrogen ion freely diffused from H+–rich clays, and the diffused hydrogen ion catalyzed the acid degradation of erythromycin A in the bulk solutions to a greater extent.
From the extrapolation curves of ln(Cs/Ce) vs. Cs, the most of homoionic clays had negative slopes, probably due to the concentration of erythromycin A molecules on the clay surfaces. High concentrations of clay-sorbed erythromycin A could act as a physical barrier causing inefficient adsorption of erythromycin A from solution to the clay surfaces. Virtually, significant deviations for the Freundlich sorption isotherms were observed with H+–exchanged kaolinite and Fe3+–exchanged montmorillonite at 500 µmol L–1 of erythromycin A.
With the equilibrium constant K0, the changes in the standard free energy (G°) of adsorption of erythromycin A were calculated in a range of –17.2 to 6.37 kJ mol–1 at 10°C and –18.3 to 3.71 kJ mol–1 at 25°C. By applying the Clausius-Clapeyron equation, the standard enthalpy (H°) of adsorption was calculated in a range of –1.55 to 7.65 kJ mol–1. Formations of clay–erythromycin A complexes were exothermic reactions, except for K+– and Fe3+–exchanged montmorillonites. Therefore, the most of clay–erythromycin A complexes were energetically stable. Except for a K+– and Fe3+–exchanged montmorillonite, the changes in the standard entropy (S°) of adsorption resulted in a positive quantity of 0.014 to 0.087 kJ mol–1 K–1, suggesting that the formation of clay–erythromycin complexes was thermodynamically favorable in the most of homoionic clay suspensions because a single molecule of erythromycin A could be replaced with a large number of solute or H2O molecules. The fact that montmorillonites had smaller quantities of S° than kaolinites indicated that the cluster of erythromycin A might be formed by ion–ion and hydrophobic interactions in the higher spacings, resulting in the decrease in the standard entropy. Therefore, erythromycin A molecules seemed to be adsorbed in the inner lattices of expandable clays (e.g., montmorillonite) as well as to the surfaces.
Clay-Catalyzed Degradation of Erythromycins A
As seen in Fig. 2A
, a part of erythromycin A was spontaneously decomposed to form anhydroerythromycin A and erythromycin A enol ether in aqueous solutions by the acid-catalyzed reactions. Erythromycin A added to cation-exchanged montmorillonites was rapidly adsorbed on clay minerals (Fig. 2B), and the clay-sorbed erythromycin A was almost completely degraded after 24 h of the equilibration (Fig. 2C and 2D). Compared with the erythromycin A degradation in aqueous solution, the rates of degradation of clay-sorbed erythromycin A were greatly enhanced by two to four orders of the magnitude. Montmorillonite was more effective for the degradation of erythromycin A than kaolinite since montmorillonite has a large surface area and a great cation-exchange capacity, which influence greatly the acidity of the clay surfaces. In this context, H+– and Fe3+–exchanged montmorillonites catalyzed the degradation of erythromycin A rapidly.
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Fig. 2. High performance liquid chromatography profiles with electrochemical detection of erythromycin A (initial concentration, 200 µg mL–1) and the degradation products from (A) the degradation in water for 72 h at 25°C, (B) the 10-min equilibration in H+–exchanged montmorillonite suspension (solid to solution ratio = 1:100), (C) the 24-h degradation by H+–exchanged montmorillonite, and (D) the 24-h degradation by Fe3+–exchanged montmorillonite. One-microampere current signals are marked at 0 and 2 min.
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The easiest way to compare the degradation products was to compare an LC/ED chromatogram with the LC/MS total ion chromatogram, since the retention times and peak intensities of individual compounds were strongly correlated between the two HPLC methods. LC/ESI-mass chromatograms helped to identify the compound peaks. With the capillary exit voltage at 200 V for collision-induced dissociation, mass spectra of all the degradation products had a base peak at m/z 158. This indicated that the desosamine moieties were intact. However, if the aminosugar was lost, the products would not be detected by positive-ion electrospray.
An LC/ED chromatogram for the erythromycin A degradation by H+–exchanged montmorillonite is shown in Fig. 2C. In this case, erythromycin A (I, m/z 734) was almost completely degraded. The largest peak, VIII, had a protonated molecule at m/z 558, and anhydroerythromycin A (II, m/z 716) was detected at the shoulder of this peak. The other major peaks, IV, VI and VII, were the protonated molecules of m/z 558, 576, and 558, respectively. The Compound Peaks V and IX were isobaric compounds of m/z 540. The ESI-mass spectrum of the Compound IX had a significant fragment ion at m/z 522 [MH+ – H2O]. In contrast, the erythromycin A degradation by Fe3+–exchanged montmorillonite was different from the degradation by H+–exchanged montmorillonite (Fig. 2D). The major degradation products were VI and VII, but the Compounds VI and VIII were produced to a lesser extent. In this case, the loss of the neutral sugar to give 5-O-desosaminylerythronolide A, that is, I
VI seemed to be a primary reaction, while the Fe3+–montmorillonite catalysis formed anhydroerythromycin A and erythromycin A enol ether to a lesser extent than the H+–montmorillonite catalysis.
To better understand the clay-catalyzed degradation of erythromycin A, the degradation of individual Compounds I, II, and III were catalyzed by H+–exchanged montmorillonite, and the LC/ESI-mass chromatograms of the isobaric compounds of m/z 540 and 558 were compared. As seen in Fig. 3
, the isobaric Compounds V and IX of m/z 540 were differently produced from the degradation of individual erythromycins A. The Compound IX seemed to be produced via Compound VIII from the degradation of Compound II, since the degradation of Compound II gave no production of Compound V (Fig. 3A). Compound V was produced similarly from the degradation of Compounds I and III (Fig. 3B and C). The results indicated that the Compound IX was 5-O-desosaminyl-10,11-anhydroerythronolide A-6,9;9,12-spiroketal(erythralosamine), which is produced by the cleavage of the neutral sugar moiety of Compound II and followed by an internal dehydration reaction, as described by Flynn et al. (1954). Less than 10% of erythromycin A and erythromycin A enol ether were degraded to 5-O-desosaminyl-8,9;10,11-dianhydroerythronolide A-9,12-hemiketal (V). A strong UV absorbance of the Compound V may be characteristic of the conjugated double bonds. Morimoto et al. (1990) also produced various 5-O-desosaminyl-8,9;10,11-dianhydro-6-O-methylerythronolide A-9,12-hemiketal compounds from the acid-degradation of 6-O-methylerythromycin A (clarithromycin).
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Fig. 3. Mass chromatograms of m/z 540 from the liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS) analyses of the H+–exchanged montmorillonite degradation products of (A) anhydroerythromycin A, (B) erythromycin A enol ether, and (C) erythromycin A.
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In Fig. 4
, there were five peaks at m/z 558 in the LC/ESI-mass chromatograms. The first three were protonated molecules of the Compounds IV, VII, and VIII, and the last two seemed to be collision-induced dissociation fragments at m/z 558 for the Compounds II and III. The clay-catalyzed degradation revealed that Compound II was degraded mainly via Compound VIII by the hydrolysis of the neutral sugar moiety (Fig. 4A). In this case, the degradation of the Compound II still had two other peaks, IV and VII, which indicated the establishment of an equilibrium between anhydroerythromycin A and erythromycin A. In contrast, the enol ether Compound III was degraded mainly via Compound IV by the hydrolysis of the neutral sugar moiety (Fig. 4B). The clay-catalyzed erythromycin A degradation was similar to that of anhydroerythromycin A (Fig. 4C). Similarly, as observed in the acid-catalyzed degradation of erythromycin A in aqueous solutions (Cachet et al., 1989), the H+–clay catalysis was ready to give Compound II by an internal dehydration reaction rather than to give the enol ether Compound III by another internal dehydration reaction and 5-O-desosaminyl-8,9-anhydroerythronolide A-6,9-hemiketal (IV) by the hydrolysis of the neutral sugar moiety.
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Fig. 4. Mass chromatograms of m/z 558 from the liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS) analyses of the H+–exchanged montmorillonite degradation products of (A) anhydroerythromycin A, (B) erythromycin A enol ether, and (C) erythromycin A.
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Summarized with the clay-catalysis, the molecular structures of erythromycin A and the putative degradation products are given in Fig. 5
, and three pathways for the clay-catalyzed degradation of erythromycin A are postulated in Fig. 6
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DISCUSSION
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Adsorption processes of erythromycin A depend on types of clays and exchanged cations. The pH of the bulk solution is important for the protonation of a weakly basic organic compound, and determines the ability to exchange with a metal cation on clays (Mortland, 1970). Clays, which have large surface areas (e.g., montmorillonites) play a major role in the adsorption of erythromycin A (Kruger, 1961; Pincke et al., 1962). Expansion of the inner lattices superficially enhances the sorption capacity because adsorbed molecules can penetrate into the interlayer spaces (Hermosín et al., 1993; Cox et al., 2000). Besides, the organic matter content and the degradation by microorganisms may be important factors influencing the biological activity, persistence, and degradation in soils (Kruger, 1961).
Protonation of the tertiary amine group of erythromycin A is facilitated by the acidity and proton-supplying power of the clay surfaces. Highly polarized H2O molecules in direct coordination with exchangeable cations, either in the clay lattices or in the adsorbed phase, may participate in the protonation of erythromycin A. A high electronegativity of exchangeable cations (e.g., K+ < Ca2+ < Fe3+ < H+) greatly affects the acidity of water dissociation (Chaussidon and Calvet, 1975). Because the acidity of clay surfaces is generally 1 to 4 units lower than the pH of the bulk solution, the proton-supplying power of the clay surfaces is so eminent that hydrated cations act as a proton-donor (Brønsted acid) on clays (Mortland and Raman, 1968; Russell et al., 1968). Polyvalent cations with unfilled d orbitals (e.g., Fe3+) are ready to form much stronger bonds with the functional groups of organic compounds (e.g., carboxyl and amino groups) than alkali and alkaline earth metal cations (Mortland, 1970). Fe3+ and H+ ions are effective for the water dissociation and the protonation of erythromycin A, whereas Ca2+ and K+ ions do not behave as strong proton-donors.
Thermodynamically, the adsorption of erythromycin A on clays was favorable, because the most reactions occur exothermically (H° > 0), and the formation of clay–erythromycin A complexes was mostly stable (S° > 0). Considering the hydrophobicity and the multiple functional groups of erythromycin A, the adsorption to the 2:1 clay layers could continue to coordinate with water molecules, inorganic salts, and other erythromycin A molecules in the neighborhood, as seen in the formation of monobutylin-montmorillonite complexes (Hermosín et al., 1993). The cluster formation may decrease in part the entropy of systems, as observed with K+– and Fe3+–exchanged montmorillonites (Table 3).
The clay-catalyzed degradation of erythromycin A facilitates the internal dehydration reactions to form anhydroerythromycin A and erythromycin A enol ether, the cleavage of the neutral sugar moiety, and the multiple internal dehydration reactions to form 5-O-desosaminyl-10,11-anhydroerythronolide A-6,9;9,12-spiroketal (erythralosamine) and 5-O-desosaminyl-8,9;10,11-dianhydroerythronolide A-9,12-hemiketal. The acidity of clay surfaces greatly influences the degradation of erythromycin A. The clay-catalysis is affected by types of clays and sorts of exchanged cations influencing the surface acidity.
Besides the acidity of clay surfaces, ion-dipole and coordination types of interactions between a carbonyl group of erythromycin A and a metal ion with an unfilled d orbit (e.g., Fe3+) may also influence the degradation of erythromycin A since the formation of an oxygen-to-metal ligand (e.g., –O···Fe3+) provides a single-bond character to the carbonyl bond or the lactonyl bond of erythromycin A. Particularly, Fe3+–exchanged montmorillonite seems to enhance the rate of the cleavage of the neutral sugar as a primary reaction.
As a conclusion, the formation of clay–erythromycin A complexes is an important process to mitigate the biological activity of erythromycin A effluent from use in humans and animals. Since the tert-amino sugar moiety of erythromycin A seems to be intact against the acid- and clay-catalysis under ambient conditions, soil-sorbed erythromycin A might persist for a prolonged time, similarly as tylosin with a low mobility in soil (Rabolle and Spliid, 2000). However, clay-sorbed erythromycin A loses the activity rapidly by the acid- and clay-catalyzed degradation. The adsorption processes using clays may be simply applicable in the agricultural, municipal, and industrial wastewater treatments to reduce the biological activity of erythromycin A effluent and to facilitate the clay-catalyzed degradation.
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ACKNOWLEDGMENTS
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This research was supported in part by an appointment to the Postgraduate Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the Food and Drug Administration.
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ABSTRACT
INTRODUCTION
during the sorption of erythromycin A on clays.