Rapid screening of Cu⁺-intermediates by using ⁶³Cu⁺ or ⁶⁵Cu⁺ ions as catalysts with or without ligand protection in Cu(I)-catalyzed azide–alkyne cycloaddition was realized using an on-line modified ICP-MS/MS platform in this work, while the Cu⁺-intermediates without ligand protection are very active, which are extremely difficult to be observed using other existing techniques. This universal platform was suitable to study the mechanism of organic reactions catalyzed by unstable metal(I) ions as well as to discover new candidates for metal(I) catalysts.