In order to explore the sensitivity enhancement of derivatization reagents for thiol compounds with respect to liquid chromatography-mass spectrometry (LC-MS) analysis, the electrospray ionization (ESI)-MS of tiopronin (TP) derivatives (TP-MA, TP-IBA, TP-AMD, TP-DMAE, TP-TFE, TP-AA and TP-AMDSA ; Fig. ) obtained from the Michael addition reaction using seven structurally diverse acrylic acid analogues was investigated. This study focused on the molecular ion species of TP derivatives and those response characteristics observed in LC-MS using four mobile phases that contained commonly used modiÐers (triÑuoroacetic acid, acetic acid, ammonium acetate and ammonium hydroxide). It was found that TP-DMAE gave an intense [ M + H ] ' ion in all the mobile phases in the positive ion mode and its response was the highest among all of the TP derivatives owing to the high proton affinity of a dimethylamino group. The other TP derivatives gave di †erent molecular ion species and lower responses based on the mobile phase used. The formation of a dominant [ M Ô H ]ion of TP-AMDSA was observed in all the mobile phases owing to the high acidity of a sulfonic acid group in the negative ion mode. TP-TFE also gave strong ion responses because it contains a high electronegative group in the negative ion mode. The ion intensities of most of the TP derivatives could be enhanced by the addition of acetic acid and ammonium hydroxide to the mobile phase and suppressed by the addition of triÑuoroacetic acid and ammonium acetate in both ionization modes. These di †erences based on the mobile phase modiÐers used were strongly related to the ESI spray current on the ES capillary.