N-in-one determination of retention factors for drugs by immobilized artificial membrane chromatography coupled to atmospheric pressure chemical ionization mass spectrometry

Immobilized artificial membrane (IAM) chromatography is widely used in drug discovery for ranking the absorption properties of drug candidates. In thi s work an IAM chromatography method using atmospheric pressure chemical ion ization mass spectrometric detection (IAM/APCI-MS) was developed for the de termination of log k(IAM) values for a mixture of compounds (9-in-one). Val ues were calculated from isocratic runs (0, 10, 20, 30, 35% acetonitrile) i n both positive and negative modes. Good correlation (r(2) = 0.97) was achi eved for n-in-one results obtained with ammonium acetate buffer and mass sp ectrometry, compared with the traditional method involving single compound analysis with phosphate buffered saline and an ultraviolet detector. A grad ient elution method providing fast determination of relative log k(IAM) val ues in a single IAM/APCI-MS run was demonstrated for the same compounds. Co pyright (C) 2001 John Wiley & Sons, Ltd.