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 interference from acetaminophen, a widely prescribed drug for headaches.


METHODS
Plasma samples were obtained from 48 subjects (23 males, 25 females; mean age, 49 +/- 14 years; hypertension, n = 37) under resting conditions. Following extraction on solid-phase cation-exchange columns, unconjugated metanephrines were analyzed by HPLC with electrochemical detection and with 4-hydroxy-3-methoxybenzylamine as an internal standard. Catecholamines were measured by HPLC.


RESULTS
The assays were linear up to 2000 pg for NMN and for MN. Intraassay 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 17 fmol for MN. Ingestion of acetaminophen or its addition to plasma did not interfere with the MN peaks. Plasma NMN and MN were positively correlated (r = 0.52 and 0.49, respectively; P <0.01 for both) with the respective catecholamines. Plasma NMN (r = 0.27; P = 0.02) but not MN positively correlated with age, whereas only plasma catecholamines (and not metanephrines) were positively correlated (P <0.05) with diastolic blood pressure.


CONCLUSIONS
This sensitive MN assay is not affected by simultaneous acetaminophen medication, and reveals a correlation of metanephrines with plasma and urinary catecholamines and age but not with blood pressure.
Roden
M
M
Division of Endocrinology and Metabolism, Department of Medicine III, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria. michael.roden@akh-wien.ac.at
Raffesberg
W
W
Raber
W
W
Bernroider
E
E
Niederle
B
B
Waldhäusl
W
W
Gasic
S
S
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood*; D008875:Middle Aged; D009647:Normetanephrine / Q000097:blood*; D010673:Pheochromocytoma / Q000097:blood / Q000175:diagnosis
D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D009647:Normetanephrine; D000082:Acetaminophen; D008676:Metanephrine