Analysis of urinary metanephrines by reversed-phase high-performance liquid chromatography and electrochemical detection

Bertani-Dziedzic, Laura; Krstulović, Ante M.; Dziedzic, Stanley W.; Gitlow, Stanley E.; Cerqueira, Sandra

doi:10.1016/0009-8981(81)90293-x

Cited by 22 publications

(6 citation statements)

References 15 publications

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“…Today's tests of catecholamine excess used to diagnose pheochromocytoma include measurements of catecholamines and metanephrines in urine or plasma and VMA in urine (Table 1). Colorimetric measurements of total metanephrines, representing the sum of normetanephrine and metanephrine determined together as a single analyte, have been superseded by HPLC measurements of fractionated normetanephrine and metanephrine 20. Liquid chromatography coupled with mass spectrometry represents a more recent advance that offers higher analytical specificity, thereby avoiding many of the pitfalls associated with drug or dietary interferences 21.…”

Section: Advances In Diagnosis: Focus On the Metanephrinesmentioning

confidence: 99%

New Advances in the Biochemical Diagnosis of Pheochromocytoma

Lenders

Pacák

Eisenhofer

2002

Annals of the New York Academy of Sciences

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Pheochromocytomas are dangerous tumors that, although a rare cause of hypertension, require consideration among large numbers of patients. The resulting low prevalence of the tumor among tested populations and the inadequacies of commonly used biochemical tests make excluding or confirming the tumor an often difficult and time-consuming task. Recognition that catecholamines are metabolized to free metanephrines within pheochromocytoma tumor cells, and that this process is independent of catecholamine release, provides a rationale for use of these metabolites in the biochemical diagnosis of pheochromocytoma. Here we briefly review the history of biochemical diagnosis of pheochromocytoma in relation to recent data about the diagnostic utility of plasma free metanephrines for detection of these tumors. Measurements of urinary or plasma catecholamines have reasonable sensitivity for detection of most pheochromocytomas, particularly those in patients with sustained hypertension. False-negative test results can, however, occur in asymptomatic patients tested because of an adrenal incidentaloma or a familial predisposition for pheochromocytoma, or when sampling is carried out between episodes of paroxysmal hypertension. Measurements of urinary total metanephrines or vanillylmandelic acid are less reliable and are of little value as initial screening tests. In contrast, measurements of plasma concentrations or free metanephrines or 24-hour urinary outputs of fractionated normetanephrine and metanephrine almost always reveal the tumor. Although, both tests have similarly high sensitivity, the relatively low specificity of urinary fractionated metanephrines means that pheochromocytomas can be more efficiently excluded or confirmed using measurements of plasma free metanephrines.

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Section: Advances In Diagnosis: Focus On the Metanephrinesmentioning

confidence: 99%

New Advances in the Biochemical Diagnosis of Pheochromocytoma

Lenders

Pacák

Eisenhofer

2002

Annals of the New York Academy of Sciences

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“…Total urinary metanephrines are usually measured after an acid hydrolysis step or more rarely by enzyme treatment with arylsulfatase to cleave the sulfate moiety from the phenolic group [7][8][9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…Metanephrines in free form are measured by HPLC with electrochemical or fluorimetric detection, using calibrators prepared inhouse by weighting free synthetic metanephrines or using certified calibrators provided by commercial distributors such as BioRad, Chromsystems or RECIPE [7][8][9][10][11][12][13][14][15][16][17]. It has been reported that most metanephrines present in calibrators and quality controls are free rather than sulfoconjugated forms [18].…”

Section: Introductionmentioning

confidence: 99%

“…Further adaptations led to routine procedures in clinical laboratories where acidic treatment at pH values ranging from 0.5 to 1.1 and incubation time from 20 to 45 min are commonly applied [7][8][9][10][11][12][13][14][15][16][17]. The problem is that, should shortcomings occur at this step (e.g., insufficient acidification), or should this step be omitted, the commercially available quality control samples will fail to alert the analyst.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic calibrators for the analysis of total metanephrines in urine: Revisiting the conditions of hydrolysis

Simonin

Gerber‐Lemaire

Centeno

et al. 2012

Clinica Chimica Acta

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Background: The quantification of total (free + sulfated) metanephrines in urine is recommended to diagnose pheochromocytoma. Urinary metanephrines include metanephrine itself, normetanephrine and methoxytyra-mine, mainly in the form of sulfate conjugates (60-80%). Their determination requires the hydrolysis of the sul-fate ester moiety to allow electrochemical oxidation of the phenolic group. Commercially available urine calibrators and controls contain essentially free, unhydrolysable metanephrines which are not representative of native urines. The lack of appropriate calibrators may lead to uncertainty regarding the completion of the hy-drolysis of sulfated metanephrines, resulting in incorrect quantification. Methods: We used chemically synthesized sulfated metanephrines to establish whether the procedure most fre-quently recommended for commercial kits (pH 1.0 for 30 min over a boiling water bath) ensures their complete hydrolysis. Results: We found that sulfated metanephrines differ in their optimum pH to obtain complete hydrolysis. Highest yields and minimal variance were established for incubation at pH 0.7-0.9 during 20 min. Conclusion: Urinary pH should be carefully controlled to ensure an efficient and reproducible hydrolysis of sul-fated metanephrines. Synthetic sulfated metanephrines represent the optimal material for calibrators and pro-ficiency testing to improve inter-laboratory accuracy.

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“…In this respect the excretion of the 3-0-methylated catecholamine metabolites can largely be attributed to the action of COMT on catecholamines secreted into the bloodstream, making their determination of considerable diagnostic importance particularly for patients with phaeochromocytoma. Numerous methods have been described for the determination of 3-0-methylated catecholamines in urine including advanced methods such as high performance liquid chromatography with fluorimetric (31, ultraviolet ( 4 ) and electrochemical detection (5) and gas chromatography with flame ionisation ( 6 ) , electron capture (7) and mass spectrometric After standing at room temperature for 15 min., the solvents were removed under reduced pressure. The yellow residues were washed with 2x20 ml of diethylether.…”

Section: F a J Muskiand At Azmentioning

confidence: 99%

Synthesis of CD₃‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses

Muskiet

Pavel

Stob

et al. 1983

Labelled Comp Radiopharmac

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SUMMARYThe preparation of CD -labelled 3-methoxytyramine, normetanephrine and metanephrine from their parent catecholamines is described. The syntheses include N-maleylation, 0-methylation by dimethylsulfate-D6, removal of the protecting group by acid hydrolysis and partial purification of the reaction product. Examples of the use of the deuterium labelled 0-methylated catecholamine metabolites as internal standards for the ammonia chemical ionisation mass fragmentographic determination of their naturally occurring analogs in urine, are given. 3Key Words: CD -labelled-3-0-methylated catecholamine metabolites; mass 3 fragmentography .

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Analysis of urinary metanephrines by reversed-phase high-performance liquid chromatography and electrochemical detection

Cited by 22 publications

References 15 publications

New Advances in the Biochemical Diagnosis of Pheochromocytoma

New Advances in the Biochemical Diagnosis of Pheochromocytoma

Synthetic calibrators for the analysis of total metanephrines in urine: Revisiting the conditions of hydrolysis

Synthesis of CD₃‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses

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Analysis of urinary metanephrines by reversed-phase high-performance liquid chromatography and electrochemical detection

Cited by 22 publications

References 15 publications

New Advances in the Biochemical Diagnosis of Pheochromocytoma

New Advances in the Biochemical Diagnosis of Pheochromocytoma

Synthetic calibrators for the analysis of total metanephrines in urine: Revisiting the conditions of hydrolysis

Synthesis of CD3‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses

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Synthesis of CD₃‐labelled 3‐methoxytyramine, normetanephrine and metanephrine for use as internal standards in mass fragmentographic analyses