Semmelweis University, Department of Pharmaceutical Chemistry, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Hőgyes E. u. 9., H-1092 Budapest, Hungary.
Eur J Pharm Sci. 2012 Jan 23;45(1-2):205-10. doi: 10.1016/j.ejps.2011.11.007. Epub 2011 Nov 18.
The complete set of experimental microscopic partition coefficients of morphine was determined for the first time for any compound. The acid-base microequilibria were characterized by combining pH-potentiometry and deductive methods using auxiliary compounds of reduced complexity. The results show around three times as many non-charged than zwitterionic microspecies in aqueous solution. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. Thus the intrinsic partition coefficients of all the microspecies could be quantitated, including the non-charged and the zwitterionic ones. The non-charged microspecies is 1070 times as lipophilic as its zwitterionic protonation isomer. Their contribution ratio to the overall lipophilicity is 3090. The lipophilicity profile of morphine was expressed, calculated and depicted in terms of species-specific lipophilicities over the entire pH range.
首次为任何化合物确定了完整的吗啡实验微观分配系数。通过结合 pH 电位法和使用辅助化合物进行演绎方法，对酸碱微平衡进行了特征描述，这些辅助化合物的复杂性降低了。结果表明，在水溶液中，非带电的微物种比两性离子微物种多约三倍。通过最相似的模型化合物模拟各个微物种的分配，然后确定并引入校正因子。因此，可以定量所有微物种的固有分配系数，包括非带电和两性离子的微物种。非带电微物种比其两性离子质子化异构体脂溶性高 1070 倍。它们对整体脂溶性的贡献比例为 3090。吗啡的亲脂性概况以整个 pH 范围内特定物种的亲脂性来表示、计算和描述。
