Secondary ion mass spectrometry (SIMS) is one of the powerful methods that can be applied to high sensitivity mass analysis and high-spatial resolution mass imaging. For the analysis of minor components of the complex biological samples, however, superior sensitivity with low background is required. We have developed an MeV-SIMS apparatus with distinctively high secondary ion yield for large organic molecules. In this study, the detection limit of our original MeV-SIMS apparatus was investigated using compounds of two lipids. In the acquired mass spectra, the molecular ions of both lipids were clearly observed with high quantitativity. In addition, the results were compared with conventional time-of-flight-SIMS results. As a result, the detection limit of MeV-SIMS apparatus was found to be below 0.1% and was much lower than that of the conventional Bi cluster SIMS. Copyright © 2014 John Wiley & Sons, Ltd.