Determination of lipophilicity for levofloxacin in the protonation equilibrium

AimTo determin the protonation equilibrium and lipophilicity for levofloxacin. MethodsThe protonation equilibrium was investigated by spectrophotometry using nonlinear regression analysis of MULTI program, then species distribution and molecular electrical property can be described accordingly. An noctanol/buffer system was exploited to determine apparent distribution coefficient (D_O/B,pH). ResultsThe dissociation constants of pK₁ and pK₂ for levofloxacin were determined as 5.85±0.04 and 8.39±0.06, respectively. Zwitterion reached the peak at isoelectric point (pI=7.12) and predominated in the physiological environment. The net electrical charge per molecule varied greatly around pI close to physiological pH for quinolones perhaps eliciting some significant changes in physicochemical and in vivo fates during drugs traversed among microcircumstances presenting different pH values. The profile of D_O/B,pH versus pH of levofloxacin had the shape of a parabolic curve and reached the maximum around pI, and ionpair effect wasn't observed for levofloxacin of tertiary amine but for grepafloxacin of secondary amine. ConclusionThe species distribution, molecular electrical property and apparent distribution coefficient of levofloxacin all demonstrated much to be reliant on pH value.