Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatography-tandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma
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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DOI：
10.1258/acb.2012.012112
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发表时间：
2013-03-01
影响因子：
2.2
通讯作者：
Eisenhofer, Graeme
中科院分区：
文献类型：
--
作者：
Peitzsch, Mirko;Prejbisz, Aleksander;Eisenhofer, Graeme
背景：血浆去甲肾上腺素（NMN）和变肾上腺素（MN）的测量为诊断嗜铬细胞瘤和副神经节瘤（PPGL）提供了灵敏的测试，但不允许检测产生多巴胺的肿瘤。在这里，我们介绍了一种基于质谱的新型方法，与超高效液相色谱 (LC-MS/MS) 相结合，用于测量 NMN、MN 和 3-甲氧基酪胺 (MTY)（多巴胺的 O-甲基化代谢物）。方法：使用通过多反应监测转变评估的特定碰撞诱导碎片离子进行识别，并根据信号强度进行定量 相对于稳定同位素标记的内标的分析物。将通过 LC-MS/MS 分析的 196 名受试者的固相提取样品的结果与通过电化学检测液相色谱 (LC-ECD) 分析的结果进行比较。将 125 名志愿者的浓度范围与 63 名 PPGL 患者（其中 14 名患有转移性疾病）的浓度范围进行了比较。结果：LC-MS/MS 方法显示出超过四个数量级的线性，分析灵敏度足以测量到 0.02 nmol/L。测定内和测定间变异系数范围为 2.8% 至 13.5%。与 LC-ECD 相比，LC-MS/MS 测得的 NMN 和 MN 分别高 17% 和 10%，MTY 低 26%。志愿者中 3-甲氧胺、NMN 和 MN 的中位数和范围分别为 0.08 (0.03-0.13)、0.35 (0.13-0.95) 和 0.15 (0.07-0.33) nmol/L。在 PPGL 患者中，有转移的患者血浆甲氧基酪胺含量比无转移的患者高六倍（1.09 与 0.19 nmol/L），并且在三名患者中，甲氧基酪胺是唯一增加的代谢物。 结论：LC-MS/MS 方法能够准确、选择性和灵敏地测量儿茶酚胺 O-甲基化代谢物，这对于筛查和管理儿茶酚胺 O-甲基化代谢物特别有用。 产生多巴胺的转移性 PPGL。
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.