Application of thermospray liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry for the identification of cynomolgus monkey and human metabolites of SK & F 101468, a dopamine D2 receptor agonist.

A combination of thermospray liquid chromatography-mass spectrometry (LC-MS) and LC MS MS has allowed the structural elucidation of a number of metabolites of 4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one (SK & F 101468) in monkey urine. By using LC-MS-MS with the third quadrupole (Q3) set up in multiple ion detection (MID) mode, a number of metabolites were subsequently detected in the human urine and plasma samples despite very low dosing regimes. This was achieved with minimal sample preparation, e.g. for the urine sample centrifugation was the only preparative step, in order to remove particulate matter, prior to analysis. The good signal-to-noise ratio obtained for the human samples, using LC MS MS with Q3 set up for MID, raised the possibility of a LC-MS-MS quantitative assay. As a result, the detection limit of this method for SK&F 101468 when dissolved in methanol was determined to be in the region of 20 pg on column.