在质子解离平衡中测定左氧氟沙星的亲脂性

目的测定左氧氟沙星的质子解离平衡和亲脂性。方法用紫外分光光度法测定质子解离平衡,并解析其水溶液中的离子分布曲线和分子荷电性质。使用正辛醇/水系统测定表观分配系数。结果两性离子在其等电点下的分布达到最大,而且其单个分子平均净电荷量对生理pH值的波动很敏感。在正辛醇/水系统中,左氧氟沙星的表观分配系数-pH值曲线呈现钟形形状,在等电点下达到峰值。结论左氧氟沙星的离子分布、分子荷电性质和表观分配系数均表现出强的pH值依赖性。

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.