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Metanephrine

(Synonyms: 间甲肾上腺素) 目录号 : GC44168

An inactive metabolite of epinephrine

Metanephrine Chemical Structure

Cas No.:5001-33-2

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产品描述

Metanephrine is a metabolite of epinephrine produced by the action of catechol-O-methyl transferase on epinephrine. [1]  Determination of plasma or urinary metanephrine is considered the principal test for the clinical diagnosis of pheochromocytoma, an adrenal medullary neuroendocrine tumor.[2] 

Reference:
[1]. Kopin, I.J., Axelrod, J., and Gordon, E. The metabolic fate of H3-epinephrine and C14-metanephrine in the rat. The Journal of Biological Chemisty 236, 2109-2136 (1961).
[2]. Wolthers, B.G., Kema, I.P., Volmer, M., et al. Evaluation of urinary metanephrine and normetanephrine enzyme immunoassay (ELISA) kits by comparison with isotope dilution mass spectrometry. Clinical Chemistry 43, 114-120 (1997).

Chemical Properties

Cas No. 5001-33-2 SDF
别名 间甲肾上腺素
化学名 4-hydroxy-3-methoxy-α-[(methylamino)methyl]-benzenemethanol
Canonical SMILES COC1=C(O)C=CC(C(O)CNC)=C1
分子式 C10H15NO3 分子量 197.2
溶解度 20mg/mL in DMSO, 20mg/mL in DMF, 20mg/mL in Ethanol 储存条件 Store at -20°C
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1 mM 5.071 mL 25.355 mL 50.7099 mL
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Research Update

Advances in Metanephrine testing for the diagnosis of pheochromocytoma

Clin Lab Med 2004 Mar;24(1):85-103.PMID:15157558DOI:10.1016/j.cll.2004.01.015.

Pheochromocytoma is a lethal tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with the symptoms of palpitations, severe headaches, and sweating. The diagnosis of pheochromocytoma is a challenging one; autopsy series suggest that many pheochromocytomas are not clinically suspected, and the undiagnosed tumor can be associated with morbid consequences. The testing of catecholamines, metanephrines, and Vanillylymandelic acid commonly is used for screening of pheochromocytoma. The diagnostic value of various biochemical tests,as reported in recent Mayo and National Institutes of Health studies, have been compared and discussed in detail. The recent developments in the methodologies of metanephrines testing also are presented.

No effect of acidification or freezing on urinary Metanephrine levels

J Endocrinol Invest 2020 Jan;43(1):53-56.PMID:31228104DOI:10.1007/s40618-019-01076-9.

Background: Urinary Metanephrine is a reliable method to estimate catecholamine secretion. Traditionally, urinary metanephrines are collected into chilled containers containing hydrochloric acid (HCl) and most laboratories freeze urinary samples before analysis. It is uncertain if these pre-analytic procedures alter Metanephrine values. Aim: To evaluate if acidifying and freezing urine samples affect the accuracy of urinary Metanephrine measurements. Methods: Random urine samples from healthy individuals were collected. Urine samples were distributed into two containers: with HCl 50% homogenized with urine to obtain pH < 2, and without HCl. Each container was divided again into aliquots for immediate measurement or freezing. One aliquot with acid (group 1) and another without acid (group 2) were sent immediately to the laboratory for testing (HPLC), while the other two aliquots, one with acid (group 3) and another without it (group 4) were frozen for 3 months at - 20 °C. Bland-Altman's test was used to analyze inter-assay agreement between measurements. Results: A total of 15 individuals were included (mean age 27.5 ± 5.9 years, 8 male and 14 white). No difference was observed on mean urinary Metanephrine/creatinine ratio between groups: group 1: 0.23 ± 0.11, group 2: 0.22 ± 0.07, group 3: 0.25 ± 0.13, group 4: 0.25 ± 0.15 mg/g creatinine; P > 0.05 for all the comparisons). Bland-Altman's analysis showed agreement between the standard method (group 1) and the experimental method (group 4). Conclusion: Measurement of urinary metanephrines by HPLC method is not influenced by sample acidification nor freezing at - 20 °C for 3 months.

Accurate Location of Catheter Tip With the Free-to-Total Metanephrine Ratio During Adrenal Vein Sampling

Front Endocrinol (Lausanne) 2022 Feb 24;13:842968.PMID:35282466DOI:10.3389/fendo.2022.842968.

Background: The selectivity index (SI) of cortisol is used to document correct catheter placement during adrenal vein sampling (AVS) in patients with primary aldosteronism (PA). We aimed to determine the cutoff values of the SIs based on cortisol, free Metanephrine, and the free-to-total Metanephrine ratio (FTMR) using an adapted AVS protocol in combination with CT. Methods: Adults with PA and referred for AVS were recruited in two hypertension centers. The cortisol and free metanephrine-derived SIs were calculated as the concentration of the analyte in adrenal veins divided by the concentration of the analyte in the distal vena cava. The FTMR-derived SI was calculated as the concentration of free Metanephrine in the adrenal vein divided by that of total Metanephrine in the ipsilateral adrenal vein. The AVS was classified as an unequivocal radiological success (uAVS) if the tip of the catheter was seen in the adrenal vein. The SI cutoffs of each index marker were established using receiver operating characteristic curve analysis. Results: Out of 125 enrolled patients, 65 patients had an uAVS. The SI cutoffs were 2.6 for cortisol, 10.0 for free Metanephrine, 0.31 for the FTMR on the left side, and 2.5, 9.9, and 0.25 on the right side. Compared to free Metanephrine and the FTMR, cortisol misclassified AVS as unsuccessful in 36.6% and 39.0% of the cases, respectively. Conclusion: This study is the first to calculate the SIs of cortisol, free Metanephrine, and the FTMR indices for the AVS procedure. It confirms that free metanephrine-based SIs are better than those based on cortisol.

Metanephrine neuroendocrine tumor marker detection by SERS using Au nanoparticle/Au film sandwich architecture

Biomed Microdevices 2016 Feb;18(1):12.PMID:26820563DOI:10.1007/s10544-016-0037-3.

Neuroendocrine tumors, such as pheochromocytoma or paraganglioma, are dangerous tumors that constitute a potential threat for a large number of patients. Currently, the biochemical diagnosis of neuroendocrine tumors is based on measurement of the direct secretory products of the adrenomedullary-sympathetic system or of their metabolites, such as catecholamines or their Metanephrine derivatives, from plasma or urine. The techniques used for analysis of plasma free metanephrines, i.e. high-performance liquid chromatography or high-performance liquid chromatography coupled with mass-spectrometry are technically-demanding and time consuming, which limit their availability. Here we demonstrate a simple, fast and low-cost method for detecting Metanephrine by Surface Enhanced Raman Scattering (SERS). The protocol consists in using evaporation-induced self-assembly of gold (Au) nanoparticles incubated with the analyte, on planar gold films. The assembly process produces regions with a dense distribution of both inter-particle gaps and particle-film gaps. Finite-difference time-domain simulations confirm that both kinds of gaps are locations of enhanced electromagnetic fields resulting from inter-particle and particle-film plasmonic coupling, useful for SERS amplification. Metanephrine vibrational bands assignment was performed according to density functional theory calculations. Metanephrine metabolite was detected in liquid at concentration levels lower than previously reported for other similar metabolites. The obtained results demonstrate that the Au nanoparticle/Au film exhibits noticeable SERS amplification of the adsorbed metabolite and can be used in the design of efficient, stable SERS-active substrates for the detection and identification of specific tumor markers.

Falsely elevated plasma Metanephrine in patients taking midodrine

Ann Clin Biochem 2018 Jul;55(4):509-515.PMID:29357678DOI:10.1177/0004563218755817.

Plasma metanephrines have become the biochemical test of choice for suspected phaeochromocytomas and paragangliomas in many institutions. We encountered two separate cases of significantly elevated plasma metanephrines in patients taking midodrine, a sympathomimetic drug used in the treatment of severe postural hypotension, in the absence of a diagnosis of phaeochromocytomas and paragangliomas. Upon stopping midodrine treatment, plasma Metanephrine concentrations returned to normal in both patients. To explore the hypothesis that midodrine or its metabolite desglymidodrine might interfere with the metanephrines assay, we tested the interaction of midodrine with Metanephrine assays from two different centres. High-performance liquid chromatography tandem mass spectrometry on plasma samples and on methanolic extract of midodrine demonstrated co-elution of the metabolite desglymidodrine with Metanephrine. We conclude that patients taking midodrine may have falsely elevated plasma Metanephrine as a result of analytical interference, and clinicians need to be aware of this problem.