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Novel transfer hydrogenation mediated reductive amination process.No HCN release during labeling reaction.Fast, non-selective labeling of all major N-glycan subclasses.One of the most frequently used high-resolution glycan analysis methods in the biopharmaceutical and biomedical fields is capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection. Glycans are usually labeled by reductive amination with a charged fluorophore containing a primary amine, which reacts with the aldehyde group at the reducing end of the glycan structures. In this reaction, first a Schiff base is formed that is reduced to form a stable conjugate by a hydrogenation reagent, such as sodium cyanoborohydride. In large scale biopharmaceutical applications, such as clone selection for glycoprotein therapeutics, hundreds of reactions are accomplished simultaneously, so the HCN generated in the process poses a safety concern. To alleviate this issue, here we propose catalytic hydrogen transfer from formic acid catalyzed by water-soluble iridium(III)- and ruthenium(II)-phosphine complexes as a novel alternative to hydrogenation. The easily synthesized water-soluble iridium(III) and the ruthenium(II) hydrido complexes showed high catalytic activity in carbohydrate labeling. This procedure is environmentally friendly and reduces the health risks for the industry. Using carbohydrate standards, oligosaccharides released from glycoproteins with highly sialylated (fetuin), high mannose (ribonuclease B) and mixed sialo and neutral (human plasma) N-glycans, we demonstrated similar labeling efficiencies for iridium(III) dihydride to that of the conventionally used sodium cyanoborohydride based reaction. The derivatization reaction time was less than 20 min with no bias towards the above mentioned specific glycan structures.