Simultaneous determination of hydrophobicity and dissociation constant for a large set of compounds by gradient reverse phase high performance liquid chromatography-mass spectrometry technique.

摘要: Fast and reliable methods for the determination of hydrophobicity acidity are desired in pre-clinical drug development phases to eliminate compounds with poor pharmacokinetic properties. Reversed-phase high-performance liquid chromatography (RP HPLC) coupled time-of-flight mass spectrometry HPLC-ESI-TOF-MS) is a convenient technique that purpose. In this work we determined chromatographic measure (logkw) dissociation constant (pKa) simultaneously large diverse group 161 drugs. Retention times were by means RP HPLC-ESI-TOF-MS series pH organic modifier gradients. We able retention 140 out (87%) compounds. For those analytes logkw pKa parameters calculated compared literature ACD Labs-calculated data. The was closely related theoretically values. Applied methodology achieved medium-throughput screening rate 100 per day proved be simple, fast approach assessing important physicochemical properties This has certain limitations as it not applicable very hydrophilic (logP<0.5) identical molar masses.