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

被引:14
作者
Tohmola, Niina [1 ,2 ]
Itkonen, Outi [2 ]
Turpeinen, Ursula [2 ]
Joenvaara, Sakari [1 ]
Renkonen, Risto [1 ,2 ]
Hamalainen, Esa [2 ]
机构
[1] Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Cent Hosp, HUSLAB, FIN-00014 Helsinki, Finland
基金
芬兰科学院;
关键词
Vanillylmandelic acid; Metanephrines; Pheochromocytoma; Paraganglioma; Neuroblastoma; LC-MS/MS; LIQUID-CHROMATOGRAPHY; PLASMA-CATECHOLAMINES; RENAL-FAILURE; HUMAN URINE; PHEOCHROMOCYTOMA; DIAGNOSIS; NEUROBLASTOMA; METABOLITES; METANEPHRINES; EXCRETION;
D O I
10.1016/j.cca.2015.03.041
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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 andmetanephrine 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 degrees C, seven days at room temperature and 98 days at - 20 degrees 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. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:206 / 212
页数:7
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