Veterinary quinolones

More then a dozen representatives of the above ring systems were introduced into the human therapy. Actisomide (2) and trequinsin (3) are used as antiarrhytmic and antihypertensive agents, respectively. Sunepitron (4), a a 2-adrenoceptor antagonist, is under clinical trials for the treatment of anxiety and depression. Representatives of the third generation of antibacterial quinolone-3-carboxylic acids the blockbluster ofloxacin (5), its levorotatory enantiomer, levofloxacin (6), and rufloxacin (7) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (8) is under development. Praziquantel (9) is widely applied for the treatment of schistosomes- and cestode-caused infection in both veterinary and human therapies (Scheme 4). 

A series of 7-diazabicycloalkyl quinolones has been prepared and found to exhibit excellent broad spectrum activity against important veterinary pathogenic bacteria [105], The structures of several of these interesting bicyclic analogues (76) as well as MIC data are summarized in Table 6.28. Compound (76e) (danofloxacin), which also exhibits excellent p.o. and s.c. activity in a mouse protection model for Pasteurella multocida [ 106], is undergoing development for use in veterinary medicine. It has been shown to exhibit excellent bioavailability properties in cattle, swine and poultry [107] and is efficacious in models for the treatment of respiratory diseases in food-producing animals [108],... 

New quinolones which contain a substituted pyrrolidinyl substituent as the amine radical in the 7-position are also currently being developed for use in veterinary medicine. These include pradofloxacin 91 with an S,S-2,8-diazabicy-clo[4.3.0]non-8-yl radical in the 7-position and a novel 8-cyano group [284,285], and premafloxacin 92 with a 3-(l-methylaminoethyl)-l-pyrrolidinyl radical in the 7-position and an 8-methoxy group [286,287]. 

Zerva L, Marshall SA, Jones RN. Prema-floxacin a projected veterinary use fluoro-quinolone with significant activity against multi-resistant gram-positive human pathogens. ]. Antimicrob. Chemother., 1996, 38, 742-744. 

Quinolone and fluoroquinolone antibiotics are a group of highly-potent, synthetic antibiotics, derived from 3-quinolone carboxylic acid They are used as broad-spectrum antibiotics in the treatment of both human and veterinary diseases. 

Literature relating to quinolones in the environment as a result of veterinary use is sparse. Trace amounts of flumequine, oxolinic acid, and sarafloxacin in sediment at fish farms have been detected. Trace amounts of enrofloxacin in soil were detected in a UK monitoring study,while studies into the sorption behavior of danofloxacin and sarafloxacin in soil showed these drugs to be non-mobile and persistent. ... 

A 2008 paper has described for the first time a dilute and shoot strategy for the simultaneous extraction of wide variety of residues and contaminants (pesticides, myco-toxins, plant toxins, and veterinary drugs) from different foods (meat, milk, honey, and eggs) and feed matrices. Several antimicrobial classes were included (sulfonamides, quinolones, P-lactams, macrolides, ionophores, tetracyclines, and nitroimidazoles) in the analytical method. Sample extraction was performed with water/acetonitrile or acetone/1% formic acid, but instead of dilution of the extracts before analysis by UPLC-MS/MS, small extract volumes (typically 5 til) were injected to minimize matrix effects. Despite the absence of clean-up steps and the inherent complexity of the different sample matrices, adequate recoveries were obtained for the majority of the ana-lyte/matrix combinations (typical values for antimicrobials were in the range of 70-120%). In addition, the use of UPLC allows high-speed analysis, since all analytes eluted within 9 min. 

Ultra-high-performance liquid chromatography has been increasingly used for the determination of multi-residue or multi-class antibiotics in food (Table 6.1). For example, an UHPLC/ESI-MS/MS method was reported to simultaneously analyze 17 different veterinary drug residues belonging to several classes of antibiotics such as macrolides, tetracyclines, quinolones, and sulfonamides... 

Another source of concern in food safety control is the increasing amounts of residues of veterinary drugs that can be found in foods. These drugs are mostly antibiotics of different structures, such as tetracyclines, macrolides, quinolones, sulphona-mides, and 6-lactams. The preferred analytical technique for antibiotic residue determination is HPLC, and specific methods for each family of antibiotics can be fovmd in the scientific literature. Most of the published methods use RP columns with gradient elution. Every available detection method can be used, depending on the application, though MS is a powerful technique for the identification and confirmation of veterinary drug residues in food samples, and at the moment, LC-MS is the method of reference. 

Antibiotics are an extremely important class of human and veterinary drugs. Chemically, they constimte a widely diverse group with different functions and ways of operation. They can be derived from living organisms or obtained synthetically. Nowadays, the term antibiotics is often extended to so-called chemotherapeutics, such as the sulfonamides and quinolones. However, aU of them exhibit antibacterial properties, i.e., either inhibit the growth of or kill bacteria. 

Sparfioxacin, 5-amino-l-cyclopropyl-7-[(3/ ,55)3,5-dimethylpiperazin-l-yl]-6,8-difluoro-4-oxo-quinolone-3-carboxylic acid, belongs to the third-generation class and is used in veterinary medicine. The TLC-densitometric method was developed... 

A multiresidue method for the analysis in egg matrices of residues of nine quinolones used in veterinary medicine has been developed (109). Two chromatographic columns were compared in that study a conventional fully porous (Inertsil C8) column and a Kinetex Cl8 core-shell colunm. Separation with the latter resulted in a significant reduction in solvent consumption and in analysis time, combined with good resolution for all analytes and better sensitivity (109). 

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