This work demonstrates the potential of inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) in trace element analysis. Aiming Hg determination in water, sample preservation requires chloride addition, which presents formation of polyatomic interfering ions as a drawback for the determination of other analytes (e.g. As and V). Thus, the effect of chloride on As, Cr, V and Hg determination and the feasibility of using ICP-MS/MS to circumvent the interference were evaluated. A standard reference material (NIST SRM 1643e) and recoveries from tap water spiked with As, Cr, Hg and V were used for accuracy assessment and for the evaluation of matrix effects. The reaction between Hg and oxygen gas is not favorable in the octopole reaction system (ORS³). Therefore, Hg was accurately determined as a single atom ion (²⁰²Hg⁺) under the same analytical conditions adopted for As, Cr and V determination by monitoring ⁷⁵As¹⁶O⁺, ⁵²Cr¹⁶O⁺ and ⁵¹V¹⁶O⁺ while the ORS³ was pressurized with oxygen gas. The oxygen reaction mode significantly improved the accuracy for As, Cr and V, especially at the lowest spiked level, which is strongly affected by matrix effects. The signal gain in m/z 75 for a solution containing 1 μg L⁻¹ As in 0.48 mol L ⁻¹ chloride medium was 1974% when employing single quadrupole mode. On the other hand, the signal increased only 7% when 0.75 mL min⁻¹ O₂ was used in mass shift mode proving the efficiency of the MS/MS mode. Thus, ICP-MS/MS and ORS³ pressurized with O₂ gas effectively reduced the interference, and enhanced the accuracy and sensitivity for some specific isotopes in a complex medium. The limits of detection for V (⁵¹V¹⁶O⁺), Cr (⁵²Cr¹⁶O⁺), As (⁷⁵As¹⁶O⁺) and Hg (²⁰²Hg⁺) were estimated to be 2, 3, 1.6 and 38 ng L⁻¹ at the 99.7% confidence level, respectively.