左旋多巴治疗帕金森病：对基于液相色谱串联质谱法的血浆和尿液中去甲变肾上腺素、变肾上腺素和甲氧基酪氨酸的测量的影响。

Levodopa therapy in Parkinson's disease: influence on liquid chromatographic tandem mass spectrometric-based measurements of plasma and urinary normetanephrine, metanephrine and methoxytyramine.

机构信息

Institute of Clinical Chemistry and Laboratory Medicine, University of Dresden, Dresden, Germany.

出版信息

Ann Clin Biochem. 2014 Jan;51(Pt 1):38-46. doi: 10.1177/0004563213487894. Epub 2013 Jul 19.

DOI:10.1177/0004563213487894

PMID:23873873

Abstract

BACKGROUND

Medication-related interferences with measurements of catecholamines and their metabolites represent important causes of false-positive results during diagnosis of phaeochromocytomas and paragangliomas (PPGLs). Such interferences are less troublesome with measurements by liquid chromatography with tandem mass-spectrometry (LC-MS/MS) than by other methods, but can still present problems for some drugs. Levodopa, the precursor for dopamine used in the treatment of Parkinson's disease, represents one potentially interfering medication.

METHODS

Plasma and urine samples, obtained from 20 Parkinsonian patients receiving levodopa, were analysed for concentrations of catecholamines and their O-methylated metabolites by LC-MS/MS. Results were compared with those from a group of 120 age-matched subjects and 18 patients with PPGLs.

RESULTS

Plasma and urinary free and deconjugated (free + conjugated) methoxytyramine, as well as urinary dopamine, showed 22- to 148-fold higher (P < 0.0001) concentrations in patients receiving levodopa than in the reference group. In contrast, plasma normetanephrine, urinary noradrenaline and urinary free and deconjugated normetanephrine concentrations were unaffected. Plasma free metanephrine, urinary adrenaline and urinary free and deconjugated metanephrine all showed higher (P < 0.05) concentrations in Parkinsonian patients than the reference group, but this was only a problem for adrenaline. Similar to normetanephrine, plasma and urinary metanephrine remained below the 97.5 percentiles of the reference group in almost all Parkinsonian patients.

CONCLUSIONS

These data establish that although levodopa treatment confounds identification of PPGLs that produce dopamine, the therapy is not a problem for use of LC-MS/MS measurements of plasma and urinary normetanephrine and metanephrine to diagnose more commonly encountered PPGLs that produce noradrenaline or adrenaline.

摘要

背景

药物对儿茶酚胺及其代谢物的测量的干扰是导致嗜铬细胞瘤和副神经节瘤（PPGL）诊断中出现假阳性结果的重要原因。与其他方法相比，液相色谱-串联质谱法（LC-MS/MS）测量时这种干扰较少，但某些药物仍会存在问题。左旋多巴是治疗帕金森病时多巴胺的前体，是一种潜在的干扰药物。

方法

对 20 名接受左旋多巴治疗的帕金森病患者的血浆和尿液样本进行 LC-MS/MS 分析，以测定儿茶酚胺及其 O-甲基化代谢物的浓度。结果与 120 名年龄匹配的对照组和 18 名 PPGL 患者进行比较。

结果

与对照组相比，接受左旋多巴治疗的患者的血浆和尿液游离和去结合（游离+结合）间甲氧基肾上腺素以及尿液多巴胺的浓度分别高出 22-148 倍（P<0.0001）。相比之下，血浆去甲肾上腺素、尿液去甲肾上腺素和尿液游离和去结合去甲肾上腺素的浓度不受影响。血浆游离甲氧基肾上腺素、尿液肾上腺素和尿液游离和去结合甲氧基肾上腺素在帕金森病患者中的浓度均高于对照组（P<0.05），但这仅对肾上腺素有影响。与去甲肾上腺素相似，在几乎所有帕金森病患者中，血浆和尿液中甲氧基肾上腺素的浓度均低于对照组的 97.5%分位数。