The simultaneous determination of hydrophobicity and dissociation constant by liquid chromatography-mass spectrometry.
作者： P. Wiczling , W. Struck-Lewicka , Ł. Kubik , D. Siluk , M.J. Markuszewski
DOI: 10.1016/J.JPBA.2014.01.038
关键词: Liquid chromatography–mass spectrometry 、 Ammonium acetate 、 Mass spectrometry 、 Dissociation constant 、 Chromatography 、 Chemistry 、 Ammonium formate 、 Electrospray ionization 、 Ammonium bicarbonate 、 Partition coefficient 、 Analytical chemistry
摘要: Abstract Convenient methods for testing drug candidates’ lipophilicity and acidity are highly requested in modern pharmaceutical research development strategies. Reversed-phase high-performance liquid chromatography (RP HPLC) might be particularly useful the determination of both dissociation constant (pH-dependent) partition coefficient related parameters, applicable high-throughput analysis multi-component mixtures. The general theory combined pH/organic modifier gradient has recently provided equations relating retention time pH mobile phase. purpose this work was to facilitate identification analytes technique by its transfer RP HPLC coupled with time-of-flight mass spectrometry electrospray ionization source (ESI-TOF-MS). accuracy proposed methodology assessed analyzing a set known drugs. ammonium formate, acetate or bicarbonate buffers were used control during chromatographic analysis. In result, p K hydrophobicity parameters determined estimated values comparing them literature data. ESI-TOF-MS allowed rapid shown especially complex use detection achieve medium-throughput screening rate (100 compounds/day) simple approach assess pharmacokinetically important physicochemical properties
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