Quantitative analysis of amino acids and acylcarnitines combined with untargeted metabolomics using ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry

Roy, Cynthia; Tremblay, Pierre-Yves; Bienvenu, Jean-François; Ayotte, Pierre

doi:10.1016/j.jchromb.2016.05.006

Cited by 31 publications

(20 citation statements)

References 47 publications

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“…This may yield in excess of 5000 ions in each ionization mode, which should not be interpreted as 5000 biological constituents, as many of these features correspond to adducts, dimers, multiply charged species, and fragment ions formed in the electrosprayer. In targeted metabolomics, specific metabolites, for example amino acids or acyl carnitines, are quantitated using stable isotope labeled standards [15]. This is frequently conducted using tandem mass spectrometry, often with a triple quadrupole mass spectrometer (TQMS), rather than a QTOFMS.…”

Section: The Need For Biomarkers Of Premalignant Liver Diseasementioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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Section: The Need For Biomarkers Of Premalignant Liver Diseasementioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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“…[28][29][30][31] Often, a development of a targeted analysis method only includes a few metabolites of interest because chemical standards can be expensive and the method installation is time consuming. [28][29][30][31] Often, a development of a targeted analysis method only includes a few metabolites of interest because chemical standards can be expensive and the method installation is time consuming.…”

Section: Introductionmentioning

confidence: 99%

“…In metabolomics, there are different method approaches available for targeted as well as untargeted applications. [28][29][30][31] Often, a development of a targeted analysis method only includes a few metabolites of interest because chemical standards can be expensive and the method installation is time consuming. Biocrates (Innsbruck, Austria) has commercially available kits for the targeted measurement of metabolites from several chemical classes; however, the kits are expensive and do not cover metabolites from groups such as organic acids or bile acids.…”

Section: Introductionmentioning

confidence: 99%

“…32 Due to uncertainty of analytes of interest, a combination of a targeted and untargeted method would be ideal to be able to quantify at least some important metabolites and have some validity of the method while maintaining the ability to screen and detect numerous unknown metabolites and features within the same method as, for In the information-dependent acquisition mode (IDA), MS/MS spectra are produced with minimal interferences as only ions within the selected narrow m/z window (typically 1-3 Da wide) are transferred to the collision cell to produce product ions. 34 Sequential window acquisition of all theoretical fragment-ion spectra (SWATH) has medium sized m/z windows (usually [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and is stepped continuously across the whole mass range of interest. SWATH obtains MS/MS data by fragmenting at a much narrower precursor ion window and retains the ability of product ion spectra recording of all precursor ions within a large mass range.…”

Section: Introductionmentioning

confidence: 99%

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Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

Boxler

Schneider

Kræmer

et al. 2018

Drug Testing and Analysis

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Over the past few years, the interest in metabolomics has increased in various fields including forensic toxicology. Forensic analysis typically requires a high degree of accuracy, which is often a problem in metabolomics applications. We aimed for a systematic evaluation of different analytical considerations of a metabolomics workflow allowing a targeted approach within an untargeted setup. Samples with 69 metabolites from different chemical classes were qualitatively and quantitatively analyzed on a high resolution quadrupole time of flight mass spectrometer coupled to liquid chromatography (UHPLC-QTOF). Three issues were addressed: (a) Two different approaches on "blind matrix" a simulated body fluid (SBF) and plasma-filtrate, were tested for calibration samples; (b) comparison of two different HPLC columns, reverse-phase (RP) and hydrophilic interaction chromatography (HILIC); and (c) comparison of three different acquisition modes (TOF-MS, information dependent data acquisition (IDA), and sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Samples were measured repeatedly for method comparison based on sensitivity, accuracy, precision, and detection robustness. The blind matricesshowed similar accuracy for most analytes, while SBF provided an easier preparation with satisfying results. To cover a wide part of the human metabolome, a combination of RP and HILIC showed the best results. The different scan modes performed equally regarding metabolite quantification while TOF-MS was more sensitive but lacked MS/MS spectra generation. IDA and SWATH files were aligned to various databases where IDA showed good MS/MS spectra matches. SWATH seemed to be beneficial in detection rate but was incompatible with many important software tools in metabolomics.

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“…Whether the concentrations of AA and AC in these neonates can offer some information about neonatal metabolic or nutritional status is still unknown. The LC/MS/MS method is an excellent tool to quantitatively detect AA and AC profiles [16,17]. In this study, the performance (precision, accuracy, and linearity) of the LC/MS/MS method was verified, and it was found that the LC/MS/MS method showed a wide linear range and satisfied precision and reproducibility in detecting AA and AC of DBS specimens.…”

Section: Discussionmentioning

confidence: 78%

Performance of LC/MS/MS in Analyzing Multiple Amino Acids and Acylcarnitines in Dried Blood Spot of Very Low Birth Weight, Low Birth Weight, and Normal Weight Neonates

Yu¹,

Han²,

Duan³

et al. 2018

Clin. Lab.

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Background: Amino acid (AA) and acylcarnitine (AC) are important biomarkers of protein and fatty acid metabolism. Examining their levels in newborns may reveal multiple inherited metabolic diseases. However, they have rarely been assessed in very low birth weight (VLBW) neonates, low birth weight (LBW) neonates and rarely been compared with normal weight (NW) neonates. The aim of the study was to identify the AA and AC profiles in dried blood spot (DBS) specimens of LBW and VLBW neonates, then compare with NW neonates, and make a contribution to the determination of cutoff values of VLBW and LBW neonates. Methods: Liquid Chromatography tandem mass spectrometry (LC/MS/MS) is an excellent tool for quantitatively detecting AA and AC profiles. This article verified the precision, accuracy, and linearity of the LC/MS/MS method in AA and AC detection, then analyzed AA and AC profiles in DBS of VLBW, LBW and NW neonates, and compared the difference of AA and AC in the three groups. Results: The results showed that the LC/MS/MS method had wide linear range, satisfied precision and reproducibility in detecting AA and AC in DBS specimens; most AA and AC concentrations significantly correlated with birth weight in DBS samples (p < 0.05). Conclusions:The results suggested that VLBW and LBW neonates have different metabolic or nutritional status with NW neonates and different AA and AC cutoffs should be defined for them to reduce the risk of false-positive cases.

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Quantitative analysis of amino acids and acylcarnitines combined with untargeted metabolomics using ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry

Cited by 31 publications

References 47 publications

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Analytical considerations for (un)‐targeted metabolomic studies with special focus on forensic applications

Performance of LC/MS/MS in Analyzing Multiple Amino Acids and Acylcarnitines in Dried Blood Spot of Very Low Birth Weight, Low Birth Weight, and Normal Weight Neonates

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