Medium molecular weight polylactides (PLAs) with different end groups were synthesized and analyzed by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. Four types of end groups were introduced as head group using appropriate initiators: cationic group [lionic liquid group (IL-PLA-OH)], easily ionizable groups [aminopyridine group (AmPy-PLA-OH) and terpyridine group (TerPy-PLA-OH)], and neutral group [butoxy group (Bu-PLA-OH)]. MALDI-TOF spectra were recorded with various cationizing agents (Li+, Na+, and K+ salts). Different modes of ionization were observed depending on the nature of end group. These various modes of ionization lead to different ionization efficiencies, which affect signal intensity. Moreover, analysis of 1/1 mixtures showed that in spectra of mixtures of IL-PLA-OH with either AmPy-PLA-OH or Bu-PLA-OH, only the signals of IL-PLA-OH were detected, while in the spectrum of AmPy-PLA-OH with Bu-PLA-OH, the former gave signals with intensity about one order of magnitude higher than the latter. Such discrimination resulting from different modes and efficiencies of ionization of macromolecules containing structurally different end groups may lead to erroneous conclusions. (C) 2016 Elsevier B.V. All rights reserved.