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ABSTRACT: Fluoroquinolones (FQLs) are synthetic antibacterial agents containing a 4-oxo-1,4-dihydroquinoline skeleton. When concomintantly administered with other drugs which may contain metal ions, particularly Al(3+) (antacids, phosphate binders, vaccines etc) they may form metal-drug complexes. Pharmacokinetic studies showed that aluminium-quinolone interactions lead to reduced bio- availability and altered activity of the drug with possible development of the toxic effects of aluminum ion. Reliable speciation in Al(3+) - quinolone systems at micromolar concentration level is needed to better understand pharmaco- and toxicokinetics of the FQLs in the presence of Al. In this work, the speciation in solutions containing Al(3+) and FQL family members (fleroxacin, moxifloxacin and ciprofloxacin) was studied by electrospray mass spectrometry (ESI-MS), ESI-MS/MS, and laser desorption ionization (LDI) MS. The dominating species identified in all the three Al(3+)-FQL solutions, at ca 30-50 µmol L(-1) total Al concentration and 2:1 to 1:3 metal-to-ligand ratio in the pH range 3.0- 6.0, were the ions related to the complexes AlL(2+), AlL(2)(+) and AlL(3)(0) (L = ligand in the monodeprotonated form). Mixed protonated and hydroxo complexes were also formed at lower and higher pH values respectively and, as expected, dimeric and polymeric species were not observed in ESI spectra. LDI measurements confirmed the existence of the mononuclear complexes found by ESI, and indicated the formation of polymeric species. The ion [2Al(3+) +5(-)](+) was identified with all three FQLs. This ionic species most probably arises from Al(2)L(2) by clustering with free ligand anions. Comparison of literature potentiometric data with mass spectral data indicated good agreement between speciation schemes. The obtained results suggest the presence of strong interaction between FQLs and Al(3+) which may be important in affecting absorption of these drugs in the gastrointestinal tract.
European Journal of Mass Spectrometry 01/2012; 18(3):313-22. · 1.21 Impact Factor
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Spectroscopy Letters 01/2005; 38(4-5):617-634. · 0.72 Impact Factor
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ABSTRACT: Toxic effects due to high aluminum body loads were observed in a number of conditions following ingestion of Al-containing antacids. Bio-availability of aluminum depends not only on the solubility of the ingested salt but also on the physico-chemical properties of the soluble Al complexes formed in body fluids. Amino acids may, upon interaction with Al-salts, form absorbable Al-complexes. Hence, complex formation equilibria between Al(3+) and either, L- histidine or L-tyrosine were studied by glass electrode potentiometric (0.1 mol/L LiCl ionic medium, 298 K), proton NMR and uv spectrophotometric measurements. Non linear least squares treatment of the potentiometric data indicates that in the concentration ranges: 0.5</=C(A1)</=2.0 ; 1.0</=C(His)</=10.0; 2.5</=PH</=6.5, in Al(3+) + His solutions, the following complexes (with log overall stability constants given in parenthesis) are formed: Al(HHis)(3+)(12.21+/-0.08); Al(His)(2+), (7.25+/-0.08); and Al(HHis)His(2+), (20.3+/-0.1). In Al(3+) + Tyr solutions in the concentration range 1.0</=C(Tyr)</=3.0 mmol/L and ligand to metal concentration ratio from 2:1 to 3:1, in the pH interval from 3.0 to 6.5 the formation of the following complexes was detected: Al(HTyr)(2+), (12.72+/-0.09); Al(Tyr)(2+), (10.16+/-0.03) and Al(OH)(2)Tyr , (2.70+/-0.05). Proton NMR data indicate that in Al(His)(2+) complex histidine acts as a monodentate ligand but its bidentate coordination is possible with carboxylate oxygen and imidazole 1-nitrogen as donors. In Al(HTyr)(3+) complex tyrosine is a monodentate ligand with carboxylate oxygen as donor. The mechanism of the formation of complexes in solution is discussed as well as their possible role in aluminum toxicity.
Metal-Based Drugs 01/2002; 8(5):235-48.
