The speciation of Cu²⁺, Ni²⁺ and Zn²⁺ ions in the presence of the fluoroquinolones (FQs) moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin, in human blood plasma was studied under physiological conditions by computer simulation. The speciation was calculated using an updated model of human blood plasma including over 6,000 species with the aid of the program Hyss2009. The identity and stability of metal-FQ complexes were determined by potentiometric (310 K, 0.15 mol/L NaCl), spectrophotometric, spectrofluorimetric, ESI-MS and ¹H-NMR measurements. In the case of Cu²⁺ ion the concentration of main low molecular weight (LMW) plasma complex (Cu(Cis)His) is very slightly influenced by all examined FQs. FQs show much higher influence on main plasma Ni²⁺ and Zn²⁺ complexes: (Ni(His)₂ and Zn(Cys)Cit, respectively. Levofloxacin exhibits the highest influence on the fraction of the main nickel complex, Ni(His)₂, even at a concentration level of 3 × 10⁻⁵ mol/L. The same effect is seen on the main zinc complex, Zn(Cys)Cit. Calculated plasma mobilizing indexes indicate that ciprofloxacin possesses the highest mobilizing power from plasma proteins, toward copper ion, while levofloxacin is the most influential on nickel and zinc ions. The results obtained indicate that the drugs studied are safe in relation to mobilization of essential metal ions under physiological conditions. The observed effects were explained in terms of competitive equilibrium reactions between the FQs and the main LMW complexes of the metal ions.

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 Al³⁺ (antacids, phosphate binders, vaccines etc.) they may form metal–drug complexes. Pharmacokinetic studies have shown that aluminium–quinolone interactions lead to reduced bio-availability and altered activity of the drug with possible development of the toxic effects of aluminium ion. Reliable speciation in Al³⁺–quinolone systems at the micromolar concentration level is needed to better understand pharmaco- and toxico-kinetics of the FQLs in the presence of Al. In this work, the speciation in solutions containing Al³⁺ and FQL family members (fleroxacin, moxifloxacin and ciprofloxacin) was studied by electrospray mass spectrometry (ESI-MS), ESI-tandem mass spectrometry and laser desorption ionisation (LDI) MS. The dominating species identified in all three Al³⁺–FQL solutions, at approx. 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 AlL²⁺, AlL₂⁺ and AlL₃⁰ (L = ligand in the mono-deprotonated 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 [2Al³⁺ + 5L⁻]⁺ was identified with all three FQLs. This ionic species most probably arises from Al₂L₂ by clustering with free ligand anions. Comparison of literature potentiometric data with mass spectral data indicated good agreement between speciation schemes. The results obtained suggest the presence of strong interaction between FQLs and Al³⁺, which may be important in affecting absorption of these drugs in the gastrointestinal tract.