Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen

Background: Pheochromocytoma is a rare cause of hypertension resulting from increased catecholamine secretion. We aimed to develop a method to measure unconjugated plasma normetanephrine (NMN) and metanephrine (MN) without in terference from acetaminophen, a widely prescribed drug for headaches. Methods: Plasma samples were obtained from 48 subjects (23 males, 25 female s; mean age, 49 +/- 14 years; hypertension, n = 37) under resting condition s. Following extraction on solid-phase cation-exchange columns, unconjugate d metanephrines were analyzed by HPLC with electrochemical detection and wi th 4-hydroxy-3-methoxybenzylamine as an internal standard. Catecholamines w ere measured by HPLC. Results: The assays were linear up to 2000 pg for NMN and for MN. Intraassa y imprecisions (CVs) were 4.7% for NMN and 7.0% for MN, and the interassay CV was 12% for both NMN and MN. The limit of detection was 11 fmol for NMN and 37 fmol for MN. Ingestion of acetaminophen or its addition to plasma di d not interfere with the MN peaks,. Plasma NMN and MN were positively corre lated (r = 0.52 and 0.49, respectively; P <0.01 for both) with the respecti ve catecholamines. Plasma NMN (r = 0.27; P = 0.02) but not MN positively co rrelated with age, whereas only plasma catecholamines (and not metanephrine s) were positively correlated (P <0.05) with diastolic blood pressure. Conclusions: This sensitive MN assay is not affected by simultaneous acetam inophen medication, and reveals a correlation of metanephrines with plasma and urinary catecholamines and age but not with blood pressure. (C) 2001 Am erican Association for Clinical Chemistry.