Ionic Cross Talk Can Lead to Overestimation of 3-Methoxytyramine during Quantification of Metanephrines by Mass Spectrometry

To the Editor:Measurements of urine or plasma metanephrine (MN)1 and normetanephrine (NMN) are considered pivotal tests in the diagnosis of pheochromocytoma and paraganglioma. There has also been increasing interest in measuring 3-methoxytyramine (3MT), the corresponding O-methylated metabolite of dopamine. 3MT measurement might allow earlier diagnosis of rare cases of pheochromocytoma and paraganglioma that secrete predominately dopamine (1,–,3). 3MT measurement might also enable stratification of familial cases by secretion patterns and play a role in predicting the malignant potential of pheochromocytoma and paraganglioma (2).Eisenhofer and others have used HPLC–electrochemical detection (HPLC-ECD) to measure 3MT in plasma (1,–,4). de Jong et al. developed an online solid-phase extraction liquid chromatography–tandem mass spectrometry (LC-MS/MS) method that simultaneously measures NMN, MN, and 3MT (5). We attempted to reproduce the latter method for plasma 3MT measurement and were initially pleased with its analytical performance. When we attempted to establish a reference interval for a healthy population, however, it became apparent that our upper reference limit of <73 pg/mL (<0.437 nmol/L) was much higher than the 1–14 pg/mL (0.006–0.084 nmol/L) interval for the published HPLC-ECD method (1). de Jong et …