The aim of this study was to investigate the applicability of a new technique using in-source collision-induced dissociation (CID) for improving quantitative linear range of various compounds in liquid chromatography-tandem mass spectrometry (LC/MS/MS). To determine whether the linear range shift due to in-source CID occurs under various MS conditions, we investigated the quantitative linear ranges of reserpine, indomethacin, and furosemide in both electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) in positive- and negative-ion detection modes. We observed 3–30-fold linear range shifts upon changing the declustering potential to adjust in-source CID in positive- and negative-ion detection modes in both ESI and APCI. These results indicated that this new technique could be applied for arbitrary adjustment of linear range regardless of ionization process and polarities in LC/MS/MS. Therefore, this technique could be applied to simultaneous quantification, in biological fluids, of compounds with quite different sensitivities under various MS conditions.