I am aiming to measure the concentration of a drug inside of cultured cells, what would be the best method for cellular lysis with solid phase extraction and HPLC-MS as downstream processes.
Lysing cells is easy simply by replacing the media with your drug extraction solvent and making sure that endogenous enzyme activity is halted by the method suitable to the drug, if the drug is sensitive to those enzymes. If extraction solvent is not directly compatible with the SPE method, evaporate the solvent in a speed-vac and reconstitute the dry sample in the SPE compatible solution. Good luck!