Abstract: The analytical methods for peptide and protein drugs in the bio-samples using liquid chromatography-mass spectrometry(LC-MS) are different from those for small molecular drugsQuantification of peptide and protein drugs is faced with many challenges because of their special physicochemical properties，such as the adsorption to solid surfaces，chemical unstable in the bio-samples,interference from endogenous substances，poor retention behaviors，special requirements on ionization sources，mass analyzers and internal standardsThis paper focuses on the common issues and counterplans on the LC-MS analysis of peptides and proteins in bio-samples.