Nitrofurantoin derivatives

Fig. 2.4. UV spectra for nitrofurantoin, showing calculation of results by First Derivative (FD). Top graph shows UV absorbance (A) versus pH. Lower graph shows dA/dpH versus pH. The pKa result (6.91) is indicated by the position of the peak maxima on the pH axis.

Rx Nitrofurantoin macrocrystals with nitrofurantoin monohydrate (Macrobid) Chemical Class Nitrofuran derivative... 

Liu, W., C. Zhao, Y. Zhang, et al. 2007. Preparation of polyclonal antibodies to a derivative of 1-amin-ohydantoin (AHD) and development of an indirect competitive ELISA for the detection of nitrofurantoin residue in water. J. Agric. Food Chem. 55 6829-6834. 

Nitro and azo compounds are reduced to amines (e.g. nitrofurantoin is reduced to its amino derivative and sulphasalazine is reduced to sulphapyridine). 

Electrochemical detectors are based upon the volta-metric oxidation or reduction of separated analytes at a micro- or thin-film electrode. A number of pharmacologically active compounds that are aldehydes, ketones, or quinones (such as doxorubicin), or nitro compounds (such as nitrofurantoin) are amenable to reduction at a mercury or platinum electrode electron-rich indole derivatives and catecholamines can be oxidized at these electrodes. An important condition that must be fulfilled for electrochemical detection to be practicable is that the mobile phase must be capable of conducting an electrical current. This makes electrochemical detection particularly useful in reversed-phase liquid chromatography, where buffered water mixed with one or more organic cosolvents is usually the mobile phase. 

Amongst forty-two furan derivatives which were investigated by Dodd and Stillman in 1944 nitrofurazone was found to be highly effective as a topical agent. It contains the azomethine side chain (—CH=N—) in the 2-position of the furan ring. From 1944 to 1960 over 450 similar compounds were synthesized and studied for antimicrobial properties. Seven compounds were selected from these, namely the commercially available compounds nitrofurazone, nifuroxime, guanofuracin hydrochloride, nitrofurantoin, furazolidone and panazone. Recently acetyl- and di-(hydroxymethyl)-derivatives of panfuran have been developed for clinical use in Japan. Some physical and chemical properties of these furan derivatives are shown in Table 6.1. 

The mechanism of antibacterial action of the furan derivatives is unknown. However, the reduced forms of nitrofurans are highly reactive and are thought to inhibit many bacterial enzyme systems, including the oxidative decarboxylation of pyruvate to acetylcoenzyme A. Nitrofurans (see list in Table 1.7) are bacteriostatic but, at high concentrations, can be bactericidal to sensitive organisms. Both chromosomal and plasmid-mediated mechanisms of resistance to nitrofurantoin occur, and these most commonly involve the inhibition of nitrofuran reductase. 

The side chain R is variable. In nitrofurantoin, the therapeutically most important derivative, it is an azomethine group (CH = N) with substituent. 

Nitrofuran drugs are synthetic broad-spectmm chemotherapeutic agents, derivatives of nitrofuran (Fig. 11). Their application in human medicine is limited to some infections (e.g., nitrofurantoin is applied in treating urinary tract infections) or to external use. In veterinary practice, they are used as growth promoters and to prevent and treat diseases in poultry and swine. 

The separations of nitrofurans have been carried out, in most instances, with a reversed phase (RP) column. As summarized in Table 1, Cig columns were selected as the analytical column for LC in most reports however, the use of a Cg, CN, and cyanopropyl-modified silica analytical column has also been described. The parent compounds, as well as their metabolites, are satisfactorily separated by Cig columns with commonly used mobile phases, such as mixtures of acetonitrile with phosphate buffer, acetate buffer, or water. The mobile phase elution for HPLC analysis can be isocratic or as a gradient system. Acetonitrile-0.1 M aqueous solution of sodium perchlorate (28 72), with 0.5% glacial acetic acid, was reported by Galeano Diaz " as an optimum mobile phase for the separation of the three nitrofuran derivatives nitrofurantoin, furazolidone, and furaltadone in milk. Lin et al." used an acetonitrile gradient with an initial hold time of 1 min at 0% acetonitrile. 

Fig. 10 Degradation characteristics of oLG tetrole derived SMP depending on the absence or presence of ethacridine lactate (EL), enoxacine (EN) and nitrofurantoin (ME), (a) Loss of relative sample mass /Xrei over time due to removal of water soluble degradation products, (b) Water uptake of samples, (c) Changes in gel content G and degree of swelling Q. (d) Alteration of the elastic modulus E (Young s modulus) of wet materials as determined by tensile tests at 37 °C in water. Reprinted from [30]. Copyright 2009, with permission from Elsevier...

Three nitrofuran derivatives, nitrofurantoin, furazolidone and furaltadone (Figure 7.7), have been measured in cow s milk after deproteinisation with TCA and SPE (ODS-modified silica). The analysis was performed using an ODS-modifed silica column with 0.5% (v/v) acetic acid in acetonitrile-aq. sodium... 

---