Development of an isotope labeling ultra-high performance liquid chromatography mass spectrometric method for quantification of acylglycines in human urine

Stanislaus, Avalyn; Guo, Kevin; Li, Liang

doi:10.1016/j.aca.2012.05.006

Cited by 32 publications

(35 citation statements)

References 21 publications

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“…This method also gives clear peaks, allowing for a wider range of metabolite analysis and has been used recently in the quantification of acylglycines, which play a crucial role in regulating inborn errors of metabolism. Using human urine samples in which these acylglycines may be found, the DmPA tag provided a LOQ as low as 1–5 nM [87]. …”

Section: Small-molecule Biomarkersmentioning

confidence: 99%

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

et al. 2012

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The identification and quantification of important biomarkers is a critical first step in the elucidation of biological systems. Biomarkers take many forms as cellular responses to stimuli and can be manifested during transcription, translation, and/or metabolic processing. Increasingly, researchers have relied upon mixed-isotope labeling (MIL) coupled with MS to perform relative quantification of biomarkers between two or more biological samples. MIL effectively tags biomarkers of interest for ease of identification and quantification within the mass spectrometer by using isotopic labels that introduce a heavy and light form of the tag. In addition to MIL coupled with MS, a number of other approaches have been used to quantify biomarkers including protein gel staining, enzymatic labeling, metabolic labeling, and several label-free approaches that generate quantitative data from the MS signal response. This review focuses on MIL techniques coupled with MS for the quantification of protein and small-molecule biomarkers.

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Section: Small-molecule Biomarkersmentioning

confidence: 99%

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

et al. 2012

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Section: Introductionmentioning

confidence: 99%

“…Differential isotope labeling (DIL) in metabolomics, pioneered by L. Li, has been exploited to address many typically encountered challenges, including matrix interference and internal standard availability [26][27][28]. Using DIL, the derivatizing reagent is synthesized into light and heavy (deuterium or 13 C-labeled) forms [29,27,30,28,[31][32][33][34][35]. The simultaneous derivatization of the analyte with both forms generates two isotopologue products that when mixed are detected as a peak pair by mass spectrometry (MS) [29,33,27,34,32,28,31,30].…”

Section: Introductionmentioning

confidence: 99%

“…Using DIL, the derivatizing reagent is synthesized into light and heavy (deuterium or 13 C-labeled) forms [29,27,30,28,[31][32][33][34][35]. The simultaneous derivatization of the analyte with both forms generates two isotopologue products that when mixed are detected as a peak pair by mass spectrometry (MS) [29,33,27,34,32,28,31,30]. Derivatizing reagents targeting specific submetabolomes, such as dansyl chloride (DNS-Cl) (alcohols, amines and phenols) [27,29], pdimethylaminophenacyl bromide (acids) [28,30], dansyl hydrazine (carbonyl) [31] and bromoacetonylquinolinium bromide (thiols) [32] are continuously introduced to DIL technique, increasing its usefulness in metabolomics.…”

Section: Introductionmentioning

confidence: 99%

“…Derivatizing reagents targeting specific submetabolomes, such as dansyl chloride (DNS-Cl) (alcohols, amines and phenols) [27,29], pdimethylaminophenacyl bromide (acids) [28,30], dansyl hydrazine (carbonyl) [31] and bromoacetonylquinolinium bromide (thiols) [32] are continuously introduced to DIL technique, increasing its usefulness in metabolomics. DIL is used for both absolute and semi quantification purposes ( Figure 1) [29,33,30,27,34,32,28,35,31]. However, absolute quantification [28,[35][36][37] has been an unfavorable option for researchers seeking rapid quantitative metabolomics data.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of accuracy and precision between multipoint calibration, single point calibration, and relative quantification for targeted metabolomic analysis

et al. 2018

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Targeted metabolomics requires accurate and precise quantification of candidate biomarkers, often through tandem mass spectrometric (MS/MS) analysis. Differential isotope labeling (DIL) improves mass spectrometric (MS) analysis in metabolomics by derivatizing metabolites with two isotopic forms of the same reagent. Despite its advantages, DIL-liquid chromatographic (LC)-MS/MS can result in substantial increase in workload when fully validated quantitative methods are required. To decrease the workload, we hypothesized that single point calibration or relative quantification could be used as alternative methods. Either approach will result in significant saving in resources and time. To test our hypothesis, six urinary metabolites were selected as model compounds. Urine samples were analyzed using a fully validated multipoint dansyl chloride-DIL-LC-MS/MS method. Samples were reprocessed using single point calibration and relative quantification modes. Our results demonstrated that the performance of single point calibration or relative quantification was inferior, for some metabolites, to multipoint calibration. The lower limit of quantification failed in the quantification of ethanolamine in most of participant samples using single point calibration. In addition, its precision was not acceptable in one participant during serine and ethanolamine quantification. On the other hand, relative quantification resulted in the least accurate data. In fact, none of the data generated from relative quantification for serine was comparable to that obtained from multipoint calibration. Finally, while single point calibration showed an overall acceptable performance for the majority of the model compounds, we cannot extrapolate the findings to other metabolites within the same analytical run. Analysts are advised to assess accuracy and precision for each metabolite in which single point calibration is the intended quantification mean.

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Acylglycine Analysis by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry (UPLC‐MS/MS)

2016

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Quantitative analysis of urine acylglycines has shown to be a highly sensitive and specific method with proven clinical utility for the diagnosis of several inherited metabolic disorders including: medium chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, short chain acyl-CoA dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, 2-methylbutyryl-CoA dehydrogenase deficiency, isovaleric acidemia, propionic academia, and isobutyryl-CoA dehydrogenase deficiency. Here, a method that is currently performed using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) is described. © 2016 by John Wiley & Sons, Inc.

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Development of an isotope labeling ultra-high performance liquid chromatography mass spectrometric method for quantification of acylglycines in human urine

Cited by 32 publications

References 21 publications

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

Relative Quantification of Biomarkers Using Mixed-Isotope Labeling Coupled With Ms

Comparison of accuracy and precision between multipoint calibration, single point calibration, and relative quantification for targeted metabolomic analysis

Acylglycine Analysis by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry (UPLC‐MS/MS)

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