A statistical approach is described to better understand the role of the matrix during a MALDI-TOFMS experiment. Potential matrix molecules were selected based on a rational experimental design and subsequently screened in order to investigate whether a certain compound can act as a matrix for synthetic polymers. The tested compounds were selected from a pool of 11 000 molecules based on descriptor calculations and a subsequent D-optimal design selection procedure. This approach selected 59 organic compounds that were then investigated for their ability to act a matrix for synthetic polymers in MALDI-TOFMS experiments. Within this contribution, we focus on the discussion of new MALDI-TOFMS matrixes that were discovered in the course of the screening. At least 10 new matrices were identified, and 5 of these were subsequently tested more closely with a variety of different synthetic polymers of different molecular weights revealing good to excellent performance of these new matrices.
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