Cisplatin (cis-[Pt(NH₃)₂Cl₂]) is a platinum-based anticancer drug used for diverse cancers. Cisplatin is commonly administered as a single drug or in combination with other drugs to raise its efficacy. Nevertheless, cancer cells could have acquired or intrinsic resistance to cisplatin. For this reason, a large number of in vitro studies have been conducted to clarify the mechanism of this phenomena. In most of these studies, dimethyl sulfoxide (DMSO) has been utilized as solvent for the stock solution of cisplatin and other drugs due to its ability to dissolve drugs in high concentration. According to a study concerning effects of solvents on the activity of cisplatin, DMSO depresses cytotoxic efficiency via ligand exchange with Cl^-. However, it remains undefined that DMSO affects which specific step and deteriorates the efficacy of cisplatin in vitro. Herein, we employed an inductively coupled plasma mass spectrometry (ICP-MS) for the quantitative analysis of cisplatin to understand how DMSO directly impedes Pt-mediated toxicity. Our quantitative results show that taken amount of cisplatin is similar regardless of the solvents (i.e. media and 0.5% DMSO in media). However, DNA-Pt adduct formation, which is a direct cause of cell apoptosis, is significantly reduced for the cells treated with cisplatin dissolved in DMSO compared to those treated with cisplatin dissolved in media. ESI-MS results also show that the reduced DNA-Pt adduction is correlated to the exchange of cisplatin with DMSO. Overall, our study would provide valuable insight into the reduced efficacy of cisplatin for cancer treatment in the presence of DMSO, based on the correlation with structural change of cisplatin induced by DMSO.