The use of high-throughput synthesis and screening techniques is demonstrated with the optimization of and the search for new antimony-rich mixed-metal oxide catalysts for the selective oxidation of isobutane to methacrolein. Three 207-member catalyst libraries have been prepared via a sol-gel synthesis procedure using design software and a synthesis robot. The catalyst libraries have been examined for catalytic activity and selectivity using spatially resolved mass spectrometry in an open-well reactor system. The reaction products have been detected by mass spectrometry and the massive data obtained have been analyzed with the help of dedicated software. Using a composition spread approach, an optimal composition of Mo-V-Sb catalysts has been identified. Screening of 68 combinations of other antimony-rich mixed oxides on libraries provides evidence that the Mo-V-Sb system is a unique ternary composition for selective oxidation of isobutane to methacrolein. Scale up of the combinatorially interesting compositions confirmed unequivocally their excellent catalytic behavior. (C) 2003 Elsevier Inc. All rights reserved.