科研之友
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摘要
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 mu mol 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 [2Al(3+)+5L(-)](+) was identified with all three FOLs. 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.
- 出版日期2012
