Pilot quality assurance programme for plasma metanephrines

Abstract

Background: Up to 2007 there was no formal external quality assurance programme for plasma free metanephrines. A pilot programme was conceived by the AACB (Australian Association of Clinical Biochemists) Working Party on biogenic amines. With support from the AACB and Royal College of Pathologists of Australasia Quality Assurance programmes, a pilot study was developed. Data from this study are presented for the first time. Methods: Twelve lyophilized plasma samples were distributed to 15 centres. Samples were spiked with metanephrine (metadrenaline), normetanephrine (normetadrenaline) and 3-methoxytyramine, all derived from human urine. Concentrations were arranged in a linear relationship. The analytes were present at six levels and samples were duplicated. Results: High-pressure liquid chromatography and tandem mass spectrometry methods showed acceptable precision but in general enzyme immunoassay displayed a higher degree of imprecision as well as a negative bias. Conclusions: Differences in calibration and matrix effects are likely to have been responsible for the discrepancy between chromatographic and immunoassay methods. These differences need to be further examined although efforts at standardization between different methods have been hampered by the lack of a universal calibrator for plasma metanephrines. Meanwhile, a laboratory's performance characteristics can be monitored and enhanced by participation in suitable external quality assurance programmes.

Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatographytandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma

“…We compared and validated the method against our routine LC-ECD method, with additional validation achieved through participation in an international quality assurance programme described elsewhere. 17 Furthermore, we validated reference intervals for the method using blood samples obtained from 125 volunteers and established preliminary diagnostic utility of the method using samples obtained from 63 patients with PPGLs, including 14 with metastatic involvement.…”

Laboratory Evaluation of Pheochromocytoma and Paraganglioma

“…This is because immunoassays suffer not only from higher imprecision than LC-ECD and LC-MS/MS methods, but also from inaccuracy involving underestimation of plasma concentrations of metanephrine and normetanephrine (27)(28)(29). As reported in an earlier study by Peaston et al (28 ), the negative bias of immunoassays can lead to repeatedly false-negative results, which by LC-MS/MS are consistently positive and appropriately indicate presence of disease.…”

“…Findings from quality assurance programs and head-to-head comparisons indicate that LC-MS/MS and LC-ECD provide comparable analytical accuracy and precision (19,27 ). Relative freedom from analytical interferences, simpler sample preparation (in some methods involving automated on-line purification), as well as rapid and high sample throughput offer significant advantages of LC-MS/MS over HPLC-ECD.…”

A 12-cm Mass with No Symptoms and Unremarkable Laboratory Results

“…Plasma free metanephrines (PMets) 6 were measured. Initial results showed borderline increases in plasma normetanephrine (NMN) and metanephrine (MN) that were not diagnostic of pheochromocytoma (PCC).…”

“…Immunoassays are also available for PMet measurement. Differences in calibration and matrix effects are believed to be responsible for the observed differences between results produced by chromatographic and immunoassay methods (6 ). Some laboratories prefer to use immunoassays, because they are simple to perform and do not require a large capital investment.…”