Evaluation of specific high-performance liquid-chromatographic determinations of urinary metanephrine and normetanephrine by comparison with isotope dilution mass spectrometry

Ann Clin Biochem 2001;38:722-730
© 2001 Association for Clinical Biochemistry


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Jacques J Willemsen,
H Alec Ross,
Bert G Wolthers,
C G J Fred Sweep and
Ido P Kema

A method for the determination of metanephrine (MN; also knownas metadrenaline), normetanephrine (NMN; also known as normetadrenaline)and 3- methoxytyramine (3-MT) in human urine using high-performanceliquid chromatography followed by electrochemical detection(ECD) was validated primarily by comparing the results withthose obtained by a gas chromatography-mass spectrometry (GC-MS)reference method. Correlation coefficients of 0.93, 0.94 and0.91 were obtained for MN, NMN and 3-MT, respectively, in agroup of healthy controls consisting of 30 women and 30 men.A systematic difference was detected only for 3-MT (- 16%).Further tests of accuracy (linearity and recovery) and precisiondemonstrated that the described method must be considered tobe a reliable approach to assess urinary metanephrines in thediagnosis of phaeochromocytoma. At lower concentrations (MN,248 nmol/L; NMN, 434 nmol/L; 3-MT, 402 nmol/L), within-assaycoefficients of variation were close to 5% or less (5·3,4·6 and 2·2%, respectively) and between-assaycoefficients of variation were 8·9, 11·2 and 12·3%,respectively, for the same low levels. This raises the possibilitythat this method can also be applied to assess urinary free,unconjugated metanephrines. Sex differences were detected forMN and NMN excretion when expressed in nmol per 24 h and nmol/mmolcreatinine, respectively, by both ECD and GC-MS methods.

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