A new pH/organic modifier gradient RP HPLC method for convenient determination of lipophilicity and acidity of drugs as applied to established imidazoline agents

作者：Wiczling Pawel; Nasal Antoni; Kubik Lukasz; Kaliszan Roman^*

来源：European Journal of Pharmaceutical Sciences, 2012, 47(1): 1-5.

DOI：10.1016/j.ejps.2012.04.021

• pH/organic modifier
• Gradient RP HPLC
• Imidazoline-like drugs
• Lipophilicity
• Acidity

Convenient drug candidates testing methods for lipophilicity and acidity are highly requested in modern pharmaceutical research and development strategy. Reversed-phase high-performance liquid chromatography (RP HPLC) might be particularly useful for the determination of both pK(a) and the apparent (pH-dependent) octanol-water partition coefficient, applicable in high-throughput analysis of multi-component mixtures. In this report the pH/organic modifier gradient RP HPLC is presented as a means of simultaneous determination of acidity and lipophilicity of a series of 26 imidazoline-like drugs. The previously theoretically elaborated approach has been applied consisting in retention measurements in a series of methanol gradient runs differing in pH range and duration of the gradient. The simultaneously determined lipophilicity and dissociation constants have been demonstrated to correlate to the respective parameters form calculation chemistry. The proposed approach can be applied to compound mixtures, it requires only minute amounts of substances, and pK(a) values can be determined in the range 3-10 units and lipophilicity log P parameter in the range 0-7 units.

• 出版日期2012-8-30