Quinolone analysis

Following their extraction and cleanup, residues of quinolone antibiotics in sample extracts can be determined by either direct nonchromatographic methods, or gas or liquid chromatographic methods. Spectrophotometric, fluorometric, or mass spectrometric detection systems have all been successfully used in quinolone analysis (Table 29.6). 

Confirmation of the identity of the suspected liquid chromatographic peaks in quinolone analysis can be made by converting the analytes to the corresponding decarboxylated derivatives and analyzing them by gas chromatography-mass spectrometry (195, 196). Most promising screening and even confirmatory methods in terms of simplicity, selectivity, and sensitivity, are those described by Munns et al. (196), Roybal et al. (188), and Eng et al. (193). 

In this chapter, an attempt has been made to present a total number of 20 QSAR models (12 QSAR models for topo I inhibitors and eight QSAR models for topo II inhibitors) on 11 different heterocyclic compound series (an-thrapyrazoles, benzimidazoles, benzonaphthofurandiones, camptothecins, desoxypodophyllotoxins, isoaurostatins, naphthyridinones, phenanthridines, quinolines, quinolones, and terpenes) as well as on some miscellaneous heterocyclic compounds for their inhibition against topo I and II. They have been found to be well-correlated with a number of physicochemical and structural parameters. The conclusion, from the analysis of these 20 QSAR, has been drawn that the inhibition of topo I is largely dependent on the hydrophobicity of the compounds/substituents. On the other hand, steric parameters (molar refractivity, molar volume, and Verloop s sterimol parameters) are important for topo II inhibition. 

The synthesis and antibacterial properties of norfloxacin (2a) were described in 1980 [65]. In this key paper in the evolution of quinolone antibacterial agents, a series of 6,7,8-polysubstituted-l-ethyl-l,4-dihydro-4-oxoquinoline-3-carb-oxylic acids (13) was synthesized, employing previously developed quantitative structure-activity relationships (QSAR) for the corresponding 6-, 7- and 8-monosubstituted derivatives versus Escherichia coli. The QSAR analysis... 

In liquid chromatographic analysis of quinolone antibacterials, most popular is the fluorometric detector due to the inherent fluorescence of these drugs and the advantages in terms of selectivity and sensitivity that this detector offers (Table 29.6). Fluorometric detection after postcolumn derivatization with sulfuric acid has also been reported (203). However, quinolones exhibit also remarkable ultraviolet absorption and are therefore ideal for direct determination without derivatization. Detection can be performed in the wavelength range of 254-295 nm. 

Fig. 29.6.1 Chromatograms obtained with UV and fluorescence detection from analysis of catfish tissue containing incurred quinolones. (Reprinted from Ref. 196. Copyright, (1995), by AOAC INTERNATIONAL.)...

CoMFA Quinolones, naphthyridinones Analysis of the effects of substituents at different positions of the quinolone/naphthyridi-none scaffold [27]... 

Gamer RC, Barker J, Flavell C et al. (2000) A validation study comparing accelerator MS and liquid scintillation counting for analysis of 14C-labelled drugs in plasma, urine and faecal extracts. J Pharm Biomed Anal 24 197-209 Hayakawa H, Fukushima Y, Kato H et al. (2003) Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters. Drug Metab Dispos 31 1409-1418... 

Providing rapid multiresidue analytical profiling is a first step toward effective quality control of herbal preparations. For example, Luo et al. [5] developed a method for the simultaneous analysis of protoberberine alkaloids, indolequinoline alkaloids, and quinolone alkaloids (Figure 13.1) extracted from the traditional Chinese medicinal... 

Further support for this observation was secured from a study of the rearrangement of the two ethers 3-allyl-4-methallyloxyquinoline and 4-allyloxy-3-methallylquinoline. The quinolone product obtained in quantitative yields in both cases was found by infrared spectral analysis to be a 1 1 mixture of the two possible structures (3 and 4). 

In a retrospective analysis, quinolone arthropathy developed during the first 3 weeks, and depended on the patient s age and history (90). It resolved fuUy within 7 days to 3 months after drug withdrawal. 

The applicability of the APCI interface is restricted to the analysis of compounds with lower polarity and lower molecular mass, compared with ESP and ISP. Applications include the LC-APCI-MS multiresidue determination of quinolone antibiotics, the determination of tetracyclines in muscle at the 100-ppb level,and the determination of fenbendazole, oxfendazole, and the sulfone metabolite in muscle at the 10-ppb level. 

Under controlled photolytic conditions, the rearranged oxidized product 273 was isolated from acetonitrile solution, and its structure was confirmed by X-ray analysis (Figure 19). Extensive photolysis led eventually to formation of di- and trimethyloxindoles, 13 and 14, a quinolone derivative, 265, and, in the case of spirooxazines, naphthoxazole 268. In the case of the two spiropyrans included in the study, 2-hydroxyl-l-naphthaldehyde and 5-nitrovanillin were also formed. It is... 

Tabernaemontana divaricata (double flower variety) provided an unusual minor alkaloid, voaharine (178), whose structure was established by X-ray analysis [137]. Voaharine is exceptional in being in all probability a tryptamine and jccologanine derived alkaloid but possessing a 3-quinolone instead of an indole chromophore. Voaharine is probably derived from voaphylline (180) (which is also present in the plant) via oxidation and rearrangement and represents the first instance of a 3-quinolone-type alkaloid obtained from Tabernaemontana. Besides these, and the known alkaloids N-methylvoaphylline (181), pachysiphine (tabersonine-P-epoxide) and apparicine, as well as two new bisindoles (vide infra), the plant also provided several new alkaloids of the aspidosperma-type including (-)-mehranine (179), voafinine (182), N-methylvoafinine (183), voafinidine (184) and voalenine (185) which were obtained in minute amounts [138-140]. 

A suspension of Lindlar s catalyst [Pd (5% on CaCOs), 213 mg, 0.10 mmol], quinolone (0.81 mL, 6.8 mmol), and the alkyne (587 mg, 2.19 mmol) in EtOAc (22 mL) was stirred for 30 min. The flask was charged with hydrogen (1 atm), and the reaction mixture was stirred until NMR analysis indicated complete conversion (14 h). The reaction mixture was filtered through Celite and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (elution with EtOAc/CILCIi, 1 5 then EtOAc) to give 487 mg (83%) of the cz.v-olefin as a white solid. 

Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients A meta-analysis. J CUn Oncol 1998 16 1179-1187. 

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