Analysis of the factors that significantly influence the stability of fluoroquinolone-metal complexes.

The aim of the present study was to evaluate factors contributing to the differences between the overall stability constants (logbeta(pqr)) of the fluoroquinolone-metal ion complexes. The experiments were performed using potentiometric titration method in wide pH range. The overall stability constants (logbeta(pqr)) were determined using the Hyperquad program. Complexation equilibria of eight different fluoroquinolones with six divalent and trivalent metal ions were investigated in this study. The authors employed a multifactorial ANOVA analysis, fixed effect model to describe the influence of particular variables affecting the stability of the analyzed complex species. Four different variables were set at different levels labeled. The ligand number (LF) was the first factor. LF determined the number of fluorochinolone molecules in the complex structure, and could take the values 1, 2 or 3. The second factor (Me) was connected with the type of the metal ion bonded in the complex. Since six different metal cations were studied, the Me factor was described with six levels. The number of hydrogen or hydroxide groups substituted into the complex molecule was the third variable (HR) with many levels labeled: q, a, s, d, f and g. The last factor FQ described the type of the fluorochinolone used for complex formations. All variables analyzed here were statistically significant (p value lower than 0.01), which indicates that all of them strongly affect the logbeta(pqr) value. Binary interactions (LF-Me, LF-FQ, Me-HR and Me-FQ) between variables were also stated, which suggests that the effects of these variables were higher than we could calculate based on the effect of each variable alone. The ANOVA analysis has shown that the following factors Me, LF and HR were the most important for the stability of the fluoroquinolone-metal ion complexes. It was also found that according to the FQ factor (type of ligand molecule) all analyzed fluoroquinolones formed stable complexes with metals. It was proved that the application of ANOVA for the entire complexation profile of analyzed fluoroquinolones with polyvalent metal ions was a valid technique for detecting the statistically significant differences in the complexation profiles. Such information may be very useful for better understanding and interpretation of differences in bioavailability of fluoroquinolones and their interactions with antacids and other multimineral drugs.