Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatography-tandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma
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Colleges, School and Institutes
BACKGROUND: Measurements of plasma normetanephrine (NMN) and metanephrine (MN) provide a sensitive test for diagnosis of phaeochromocytomas and paragangliomas (PPGLs), but do not allow detection of dopamine-producing tumours. Here we introduce a novel mass spectrometric based method coupled to ultraperformance liquid chromatography (LC-MS/MS) for measuring NMN, MN and 3-methoxytyramine (MTY), the O-methylated metabolite of dopamine.
METHODS: Specific collision-induced fragment ions assessed by multireaction monitoring transitions were used for identification, with quantification according to signal intensities of analytes relative to stable isotope labelled internal standards. Results for solid-phase extracted samples from 196 subjects analysed by LC-MS/MS were compared with those analysed by liquid chromatography with electrochemical detection (LC-ECD). Concentration ranges in 125 volunteers were compared with those from 63 patients with PPGLs, including 14 with metastatic disease.
RESULTS: The LC-MS/MS method showed linearity over four orders of magnitude with analytical sensitivity sufficient to measure to 0.02 nmol/L. Intra- and inter-assay coefficients of variation ranged from 2.8% to 13.5%. NMN and MN were respectively measured 17% and 10% higher and MTY 26% lower by LC-MS/MS than by LC-ECD. Medians and ranges for 3-methoxytramine, NMN and MN were respectively 0.08 (0.03-0.13), 0.35 (0.13-0.95) and 0.15 (0.07-0.33) nmol/L in volunteers. Among patients with PPGLs, plasma methoxytyramine was six-fold higher in patients with than without metastastases (1.09 versus 0.19 nmol/L) and in three patients was the only metabolite increased.
CONCLUSIONS: The LC-MS/MS method enables accurate, selective and sensitive measurements of catecholamine O-methylated metabolites that should be particularly useful for screening and management of dopamine-producing metastatic PPGLs.
|Number of pages||9|
|Journal||Annals of Clinical Biochemistry|
|Issue number||Pt 2|
|Publication status||Published - Mar 2013|
- Adrenal Gland Neoplasms, Adult, Aged, Blood Chemical Analysis, Chromatography, High Pressure Liquid, Dopamine, Female, Humans, Male, Metanephrine, Middle Aged, Neoplasm Metastasis, Normetanephrine, Paraganglioma, Pheochromocytoma, Reproducibility of Results, Tandem Mass Spectrometry, Young Adult