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Clin Chim Acta. 2015 Jun 15;446:206-12. doi: 10.1016/j.cca.2015.03.041. Epub 2015 Apr 18.

Preanalytical validation and reference values for a mass spectrometric assay of serum vanillylmandelic acid for screening of catecholamine secreting neuroendocrine tumors.

Author information

1
Haartman Institute, University of Helsinki, Finland; HUSLAB, Helsinki University Central Hospital, Helsinki, Finland. Electronic address: niina.tohmola@helsinki.fi.
2
HUSLAB, Helsinki University Central Hospital, Helsinki, Finland.
3
Haartman Institute, University of Helsinki, Finland.
4
Haartman Institute, University of Helsinki, Finland; HUSLAB, Helsinki University Central Hospital, Helsinki, Finland.

Abstract

BACKGROUND:

Urinary vanillylmandelic acid (VMA) is used to diagnose and monitor catecholamine secreting neuroendocrine tumors (NETs). We developed and validated a new liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for determination of serum VMA.

METHODS:

We used serum samples from healthy volunteers (n=314) and patients suspected for NET (n=36). Deuterated VMA as an internal standard was added to samples before solid phase extraction (SPE) and LC-MS/MS analysis. We studied the effects of sample storage, sampling device and a meal on serum VMA and metanephrine concentrations. Diurnal variation and age-dependent reference intervals were established. The diagnostic performance was compared with a urinary HPLC assay for VMA and metanephrines and a serum metanephrine LC-MS/MS assay.

RESULTS:

Serum VMA is stable at least for one day at +4°C, seven days at room temperature and 98 days at -20°C. Type of sampling device was not critical, but elevated serum VMA occurs after a meal (p = 0.031). Serum VMA increased with age. Therefore, we suggest clinical cut-off values of 62 nmol/L, 80 nmol/L and 108 nmol/L for age groups 18-50 yrs, 51-70 yrs and > 70 yrs, respectively. Comparison between a urinary VMA HPLC assay and serum VMA LC-MS/MS assay showed good correlation.

CONCLUSIONS:

Our LC-MS/MS assay is fast and sensitive and suits well for use in a clinical laboratory. Compared to 24-h urine collection our serum assay enables well controlled sampling and convenient preanalytical steps.

KEYWORDS:

LC–MS/MS; Metanephrines; Neuroblastoma; Paraganglioma; Pheochromocytoma; Vanillylmandelic acid

PMID:
25896957
DOI:
10.1016/j.cca.2015.03.041
[Indexed for MEDLINE]

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