Antibiotic electrodes

Several antibiotics show distinct selectivity in their interactions with alkali metal cations (Pioda and Simon, 1969). Two antibiotics in particular, nonactin and valinomycin, associate with potassium ions in preference to sodium ions. It is difficult, by conventional methods, to fabricate an electrode which is selective to potassium in the presence of sodium ions. Using the preferential behavior of these two antibiotics, Simon (1969) was able to produce -selective antibiotic membrane electrodes. 

Nonactin was suspended in Nujol/2-octanol and valinomycin was suspended in diphenylether. These solutions were respectively incorporated into liquid membrane potentiometric electrodes. The usual commercial glass electrodes exhibit a K to Na selectivity on the order of 30 1. Simon s valinomycin electrode displayed a 3800 1 selectivity for K to Na , and an 18,000 1 selectivity for K with respect to H. Thus the electrode should be useful in strongly acid media in which glass electrodes cannot be used, or are ineffective. 

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The designation membrane is used here in a very general sense, as many materials are used. Commercially available electrodes include liquid membrane units, solid-state electrodes, glass membrane electrodes, and plastic membrane electrodes. General classes of ion specific electrodes in addition to those cited are immobilized-liquid membrane electrodes, mixed-crystal membrane electrodes, enzyme electrodes, and antibiotic electrodes (Rechnitz, 1973). Certain of these membrane electrodes are now discussed in some detail. A generalized membrane electrode is illustrated in Figure 6.1a. 

M.p. 296 C. Accepts an electron from suitable donors forming a radical anion. Used for colorimetric determination of free radical precursors, replacement of Mn02 in aluminium solid electrolytic capacitors, construction of heat-sensitive resistors and ion-specific electrodes and for inducing radical polymerizations. The charge transfer complexes it forms with certain donors behave electrically like metals with anisotropic conductivity. Like tetracyanoethylene it belongs to a class of compounds called rr-acids. tetracyclines An important group of antibiotics isolated from Streptomyces spp., having structures based on a naphthacene skeleton. Tetracycline, the parent compound, has the structure ... 

Although rum ammonia levels are not routinely measured, it is a useful indicator of Reye s syndrome and should be monitored in newborns at risk of developing hyperammonemia Ammonia is produced in many analytically useful enzyme reactions and the ammonium ISE has been used as the base sensor in several enzyme electrodes (see next section). In addition to valinomycin, other antibiotics such as the nonactin homalogs and gramicidins also behave as ionophores. The nonactin homolo were originally studied for their ability to selectively bind potassiiun ions It was then discovered that ammonium ions were preferred over potassium ions, and the selectivity coefficient Knh+ = 0.12 was reported. Since ammonia is present at fairly low levels in serum, this selectivity is not sufficient to to accurately measure NH4 in the presence of K. An extra measure of selectivity can be gained by using a gas permeable membrane to separate the ammonia gas from the sample matrix... 

Capillary zone electrophoresis coupled with fast cyclic voltammetric detection was developed by Zhou et al. [27] for the separation and determination of OTC, TC, and CTC antibiotics. All compounds were well separated by optimization of pH and complexation with a boric acid sodium tetraborate buffer. The detection limit using fast on-line cyclic voltammetric detection with Hg-film-microm electrode was 1.5 x 10-6 mol/L for OTC (signal to noise ratio > 2). A continuous flow manifold coupled on-line to a capillary electrophoresis system was developed by Nozal et al. [28] for determining the trace levels of OTC, TC, and DC in surface water samples. 

Potentiometric enzyme-based electrodes have found application in clinical, pharmaceutical, food and biochemical analyses to enable the selective determination of a wide range of important enzyme substrates, including amino acids, esters, amides, acylcholines, /Mactam antibiotics, sugars, enantioselective drugs and many others [74]. 

Fang, X. M., Ye, J. N., and Fang, Y. Z. (1996). Determination of polyhydroxy antibiotics by capillary zone electrophoresis with amperometric detection at a nickel electrode. Anal. Chim. Acta 329, 49-55. 

Yang, W. C., Yu, A. M., and Chen, H. Y. (2001). Applications of a copper microparticle-modified carbon fiber microdisk array electrode for the simultaneous determination of aminoglycoside antibiotics by capillary electrophoresis. /. Chromatogr. A 905, 309—318. 

Sqnare-wave voltammogram of antibiotic adriamycin adsorbed to the snrface of static mercnry drop electrode is shown in Fig. 3.10 [190]. It originates from the redaction of qninone gronp in the molecule. Figure 3.11 shows the dependence of the... 

A different direction in ion-selective electrode research is based on experiments with antibiotics that uncouple oxidative phosphorylation in mitochondria [59]. These substances act as ion carriers (ionophores) and produce ion-specific potentials at bilayer lipid membranes [72]. This function led Stefanac and Simon to obtain a new type of ion-selective electrode for alkali metal ions [92] and is also important in supporting the chemi-osmotic theory of oxidative phosphorylation [69]. The range of ionophores, in view of their selectivity for other ions, was broadened by new synthetic substances [1,61]. 

The Ba ISE containing the acyclic membrane carrier nonylphenoxy-poly(ethylenoxy)ethanol described by Levins [123] opened new fields in ion-selective electrodes based on synthetic acyclic ionophores. Simon and coworkers synthesized several hundred substances [3] that can be used for ISEs to determine alkaline earth ions, primarily Ca [4], and also [190], etc. (for a review, see [133, 154]). A natural ionophore for calcium is the antibiotic,... 

Thus, the system comprising membrane, solution 2 of constant composition (internal filling solution), and electrode 2 (internal reference electrode) constitutes an ion selective electrode. The electrically neutral carrier antibiotics of the valinomycin group and related lipid-soluble compounds can serve as the active components of highly selective liquid... 

Since 1966, when Stefanac and Simon (3) developed the first electrodes of this type containing macrotetrolides, valinomycin, and other antibiotics as the active components, the analytical potential of these ion selective sensors has been generally recognized, and forms incorporating various electrically neutral ligands specific for K+ (3,86,87,89,107—110, 118, 119), NHj 85, 112), Ba2+ 113, 114), and other cations 115, 117) have found practical application (Table 9). 

The effect of ligands on the character and degree of the inner-sphere reorganization during electroreduction of aqua-, aquahydroxy-, hydroxy-, and ethylene-diamine tetraacetic acid (EDTA) complexes of Zn(II) [95] and electrochemical process of Zn(II) complexed by different ligands - glycinate [96], ethanol amine [97], azinyl methyl ketoximes [98], aspartame [99], glutathione [100, 101] and several cephalosporin antibiotics [102] -were studied at mercury electrodes in aqueous solutions. 

Nucleotides - [AMINO AC IDS - L-MONOSODIUM GLUTAMATE (MSG)] (Vol 2) -as antibiotics [ANTIBIOTICS - NUCLEOSIDES AND NUCLEOTIDES] (Vol 3) -catabolism of [MINERALNUTRIENTS] (Vol 16) -electrodes for [BIOPOLYMERS - ANALYTICAL TECHNIQUES] (Vol 4) -phosphorus nmr [MAGNETIC SPIN RESONANCE] (Vol 15) -as radioactive tracers [RADIOACTIVETRACERS] (Vol 20)... 

This principle is applied for the potential development in the EPMEs and for obtaining the intensity of the current in amperometric immuno-sensors. For the enantioselective, potentiometric electrodes, it is necessary to find a molecule with a special architecture that can accommodate the enantiomer. In this regard, cyclodextrins and their derivatives, maltodextrins, antibiotics and fullerenes and their derivatives were proposed [17-52]. 

The main components of the membrane of the enantioselective, potentiometric electrode are chiral selector and matrix. Selection of the chiral selector may be done accordingly with the stability of the complex formed between the enantiomer and chiral selector on certain medium conditions, e.g., when a certain matrix is used or at a certain pH. Accordingly, a combined multivariate regression and neural networks are proposed for the selection of the best chiral selector for the determination of an enantiomer [17]. The most utilized chiral selectors for EPME construction include crown ethers [18-21], cyclodextrins [22-35], maltodextrins 136-421, antibiotics [43-50] and fullerenes [51,52], The response characteristics of these sensors as well as their enantioselectivity are correlated with the type of matrix used for sensors construction. 

Two EPMEs based on macrocyclic glycopeptide antibiotics—vancomycin and teicoplanin—were designed for the assay of acetyl-L-carnitine [44]. The linear concentration ranges for the proposed electrodes were 10 5-10-2 mol/L for the vancomycin-based electrode and 10 4-10-2 mol/L for the teicoplanin-based electrode, with slopes of 58.1 and 55.0mV/p(acetyl-L-camitine), respectively. The enantioselectivity was determined over D-carnitine. 

Two EPMEs were proposed for the assay of R-baclofen. The electrodes were designed using macrocyclic glycopeptide antibiotic, teicoplanin [45]. Acetonitrile was added to the teicoplanin to design a modified teicoplanin-based electrode. The linear concentration ranges for the proposed enantioselective, membrane electrodes were 10 7-10 4mol/L for teicoplanin-based electrode and 10 6-10 4mol/L for the electrode based on teicoplanin modified with acetonitrile. The slopes of the electrodes were 60.0 and 57.2 mV/pR-baclofen for teicoplanin and teicoplanin modified with acetonitrile-based electrodes, respectively. The enantioselectivity was determined over S-baclofen. The proposed electrodes can be employed reliably for the assay of R-baclofen raw material and from its pharmaceutical formulation, Norton-Baclofen tablets. 

EPMEs based on carbon paste modified with antibiotics vancomycin, teicoplanin and teicoplanin modified with acetonitrile are proposed for the determination of d-2-HGA [47]. The proposed electrodes can be used reliably for enantiopurity tests of d-2-HGA using direct potentiometric method of analysis. The linear concentration ranges recorded for EPMEs are 10 7-10 3, 10 7-10 2 and 10 6-10 2 mol/L with detection limits of 1.00 x 10 8, 1.00 x 10 8 and 1.00 x 10 7 mol/L for the vancomycin, teicoplanin and teicoplanin modified with acetonitrile-based EPME, respectively. The selectivity was determined over l-2-HGA, creatine, creatinine and some inorganic cations. The proposed EPMEs were applied for the assay of d-2-HGA in urine samples. The duration of one analysis is 10 min, including the calibration of the instrument and the determination of the amount of d-2-HGA in the urine sample. 

Three EPMEs based on macrocyclic glycopeptide antibiotics— vancomycin and teicoplanin (modified or not with acetonitrile)—were proposed for the determination of l- and D-enantiomers of methotrexate (Mtx) [48]. The linear concentration ranges for the proposed enantioselective membrane electrodes were between 10 6 and 10-3 mol/L for l- and D-Mtx. The slopes of the electrodes were 58.00 mV/pL-Mtx for vancomycin-based electrode, 57.60 mV/pD-Mtx for teicoplanin-based electrode and 55.40 mV/pD-Mtx for teicoplanin modified with acetonitrile-based electrode. The detection limits of the proposed electrodes were of 10 8 mol/L magnitude order. All proposed electrodes proved to be successful for the determination of the enantiopurity of Mtx as raw material and of its pharmaceutical formulations (tablets and injections). 

An EPME based on carbon paste impregnated with macrocyclic antibiotic vancomycin as chiral selector was proposed for the enantioanal-ysis of S-perindopril raw material and from its pharmaceutical formulation [49]. The proposed electrode was applied for the assay of... 

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