AbstractTwo general schemes for the synthesis of isotope labelled monomethyl catecholamine metabolites are described. Catechol was converted to 2‐methoxy‐d3‐phenol (2) with deuteromethyl iodide and reacted with sodium glyoxylate to form 4‐hydroxy‐3‐methoxy‐d3‐mandelic acid (3). Hydrogenolysis of the methyl ester‐diacetate of 3 with excess sodium borohydride in water yielded 4‐hydroxy‐3‐methoxy‐d3‐phenylacetic acid (4). Reduction of 3 with diborane produced 4‐hydroxy‐3‐methoxy‐d3‐phenylethylene glycol (5). An alternative route was to alkylate 3,4‐dihydroxybenzaldehyde (6) and produce 3 or its 3‐hydroxy‐4‐methoxy isomer via the nitrile mandelic acid synthesis. Suitability of these isotopic and isomeric variants as internal standards for quantitation by gas