Protein must be removed from cells before mass spectral analysis. There are a number of different protein extraction methods, but we have the found detergent lysis by sodium dodecyl sulfate (SDS) in combination with sonication most effective. Detergents disrupt/lyse the cell membrane and detergents with high ionic strength, such as SDS, also denature proteins. However, yeast have cells walls which resist detergent lysis. To overcome this barrier we sonicate the yeast cells during detergent lysis. Sonicators send intense sound waves through samples to disrupt cell walls. Cell walls weakened by detergent lyse easily when sonicated.