Targeted metabolomic analysis of plasma samples for the diagnosis of inherited metabolic disorders

Janečková, Hana; Hron, Karel; Wojtowicz, Petr; Hlídková, Eva; Barešová, Anna; Friedecký, David; Žídková, Lenka; Horník, Petr; Behúlová, Darina; Procházková, Dagmar; Vinohradská, Hana; Pešková, Karolína; Bruheim, Per; Smolka, Vratislav; Šťastná, Sylvie; Adam, Tomáš

doi:10.1016/j.chroma.2011.09.074

Cited by 52 publications

(42 citation statements)

References 12 publications

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“…A wide range of biomarkers for phenylketonuria (c.782G>A) were presented in the present study, including phenylalanine, N-acetylphenylalanine, tyrosine, phenylacetate, mandelate, o-hydroxyphenylacetate, phenyllactate, phenylpyruvate, phenylacetylglutamine and homovanillate. These biomarkers of phenylketonuria have been detected previously through mass spectrometry with electrospray ionization (15) and high-performance liquid chromatography with a GC-clamped primer combined with other analytical methods (25).…”

Section: Discussionmentioning

confidence: 99%

Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine

Sheng

Wang

2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to conduct preliminary clinical screening and monitoring using a novel two-step derivatization process of urine in five categories of inherited metabolic disease (IMD). Urine samples (100 µl, containing 2.5 mmol/l creatinine) were taken from patients with IMDs. The collected urine was then treated using a two-step derivatization method (with oximation and silylation at room temperature), where urea and protein were removed. In the first step of the derivatization, α-ketoacids and α-aldehyde acids were prepared by oximation using novel oximation reagents. The second-step of the derivatization was that residues were silylated for analysis. Urine samples were examined using gas chromatography/mass spectrometry (GC/MS) and a retention time-locking technique. The simultaneous analysis and identification of >400 metabolites in >130 types of IMD was possible from the GC/MS results, where the IMDs included phenylketonuria, ornithine transcarbamylase deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, β-ureidopropionase deficiency and mitochondrial metabolic disorders. This method was demonstrated to have good repeatability. Considering α-ketoglutarate (α-KG) as an example, the relative standard deviations (RSDs) of the α-KG retention time and peak area were 0.8 and 3.9%, respectively, the blank spiked recovery rate was between 89.6 and 99.8%, and the RSD was ≤7.5% (n=5). The method facilitates the analysis of thermally non-stable and semi-volatile metabolites in urine, and greatly expands the range of materials that can be synchronously screened by GC/MS. Furthermore, it provides a comprehensive, effective and reliable biochemical analysis platform for the pathological research of IMDs.

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Section: Discussionmentioning

confidence: 99%

Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine

Sheng

Wang

2017

Experimental and Therapeutic Medicine

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“…Thus analysis, and especially the quantitative determination, of these important metabolite groups is of high interest, not only for increased understanding of function and properties of biological systems, but also for applications such as in food science and clinical diagnosis. For example, many diseases with altered amino and/or organic acid metabolism are known [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Quantitative Analysis of Amino and Organic Acids by Methyl Chloroformate Derivatization and GC-MS/MS Analysis

Kvitvang

Kristiansen

Lien

et al. 2014

Methods in Molecular Biology

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Alkyl chloroformates are known for their ability to produce mixed anhydrides, and they have found use as versatile derivatization reagents for gas chromatographic (GC) separation of amino- and organic acids. Triple-quadrupole mass spectrometers are excellent detectors for high sensitive and selective analysis. Here, we describe a methyl chloroformate (MCF) GC-MS/MS method for the quantitative analysis of metabolites containing amino- and/or carboxylic groups. The method covers over 60 metabolites with quantitation limits down to the low picomole range injected on column, and any metabolite with amino- and/or carboxylic acid functional groups that yield a stable and volatile MCF derivative can be included in the method. Absolute quantitation can be achieved by including a stable isotope-coded derivatization agent (d3-MCF) and deuterated alcohol solvent (e.g., d4-methanol). As the carboxylic and amino groups are differently labeled, the former from the solvent methanol while the latter from MCF, this approach can also be used to identify a number of amino and carboxylic groups in unknown analytes in an extract.

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“…It is a well established approach in the diagnosis of inherited metabolic disorders. 16 This can be explained from the following study done to assess early markers of insulin resistance (IR). Insulin resistance is a risk factor for type 2 diabetes mellitus and cardiovascular disease progression.…”

Section: Non-targeted Analysismentioning

confidence: 99%

Metabolomics - the new "omics" of health care

Vs¹,

PVLN²,

Bitla³

2012

JCSR

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Metabolic diseases are caused by chronic dysregulations of metabolism that differ among individuals due to interactions of the genetic and environmental influences manifesting as a particular phenotype. These are usually diagnosed with the help of individual metabolites which serve as disease biomarkers. However, single biomarker based diagnostics for metabolism-based diseases fails to identify the cause of the alteration of these surrogate markers. This is where metabolomics comes into the clinical picture as it not only helps in assessing the risk of an individual for developing a particular disease but also helps in individualizing therapy based on the metabolic defect. Metabolomics is named in line with other recently developed approaches of diagnostics, i.e., genomics and proteomics. This review provides an overview of the fundamental basic principles, the techniques involved and the applications of this new -omics of healthcare. Keywords: Metabolic disorders, Metabolomics, Health careKiranmayi VS, Srinivasa Rao PVLN, Bitla AR. Metabolomics -the new "omics" of health care. J Clin Sci Res 2012;3:131-7.

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Targeted metabolomic analysis of plasma samples for the diagnosis of inherited metabolic disorders

Cited by 52 publications

References 12 publications

Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine

Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine

Quantitative Analysis of Amino and Organic Acids by Methyl Chloroformate Derivatization and GC-MS/MS Analysis

Metabolomics - the new "omics" of health care

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