Updated project metadata. Analysis of cells and tissue by bottom up proteomics starts with lysis, followed by in-solution digestion. Lysis buffers commonly used include detergents and other reagents for efficient solubility of the proteins. However these reagents are, for the most part, incompatible with downstream analytical instrumentation. One method for in-solution digestion and cleanup, termed Suspension Trapping (S-Trap), has been recently introduced. We present evaluation of the compatibility of commonly used lysis buffers with S-trap: SDS, urea, NP-40, RIPA and SDS with DTT (SDT). We show that S-trap is compatible with all the tested buffers, with SDS and SDT performing the best. Based on this data, we anticipate that the method will transform experimental planning for mass spectrometry based proteomics, making it far more flexible and tolerable of various lysis buffers.