To the Editor: Wright et al. (1) recently described the use of multiple reaction monitoring with multistage fragmentation (MRM3), for which the conventional product ion produced by collision-induced fragmentation of the precursor ion [M+H+] is further fragmented in an ion trap to produce a “second generation product ion.” This approach can eliminate occasional interferences during measurements of metanephrines from unknown substances in plasma samples. We outline here interference from an endogenous analyte present in all plasma samples, 3-O-methyldopa, which cannot be eliminated by MRM3. The interference affects measurements of methoxytyramine, the O-methylated metabolite of dopamine, important for diagnosis of chromaffin cell tumors and identification of metastatic disease (2, 3). 3-O-Methyldopa is formed by the action of catechol-O-methyltransferase (COMT) on l-dopa, the immediate precursor of dopamine. 3-O-methyldopa is present in plasma at 50–300 nmol/L (10–63 ng/mL) concentrations (4), more than 10-fold higher than l-dopa, reflecting slow renal clearance. In contrast, concentrations of methoxytyramine normally do not exceed 0.11 nmol/L (18 pg/mL), with cutoffs of 0.20–0.41 nmol/L (33–69 pg/mL) described for diagnosis of metastatic disease (3).
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Peitzsch et al. (2015) studied this question.