Kinetic and molecular orbital analyses of dicarboxylic acylcarnitine methylesterification show that derivatization may affect the screening of newborns by tandem mass spectrometry

Maeda, Yasuhiro; Nakajima, Yoko; Gotoh, Kana; Hotta, Yuji; Kataoka, Tomoya; Sugiyama, Naruji; Shirai, Naohiro; Ito, Tetsuya; Kimura, Kazunori

doi:10.1016/j.bmcl.2015.11.016

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…With the same SPE plate isolation, 65 acylcarnitines were separated [76]. Although MCX SPE cartridges have been widely used in the extraction of acylcarnitines, it must be noted that the sulfo group on the packing could catalyse the carboxylic acid groups of about 40% dicarboxylic acylcarnitines reacting with MeOH in the elution solvent to form methylation products [77,78]. Therefore, Li et al suggested that using ACN (containing 5% NH 4 OH) instead of MeOH as elution may avoid the methylation problems [79].…”

Section: Detection Of Acylcarnitines In Biological Samplesmentioning

confidence: 99%

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

2019

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Acylcarnitines play an essential role in regulating the balance of intracellular sugar and lipid metabolism. They serve as carriers to transport activated long-chain fatty acids into mitochondria for β-oxidation as a major source of energy for cell activities. The liver is the most important organ for endogenous carnitine synthesis and metabolism. Hepatocellular carcinoma (HCC), a primary malignancy of the live with poor prognosis, may strongly influence the level of acylcarnitines. In this paper, the function, detection and alteration of acylcarnitine metabolism in HCC were briefly reviewed. An overview was provided to introduce the metabolic roles of acylcarnitines involved in fatty acid β-oxidation. Then different analytical platforms and methodologies were also briefly summarised. The relationship between HCC and acylcarnitine metabolism was described. Many of the studies reported that short, medium and long-chain acylcarnitines were altered in HCC patients. These findings presented current evidence in support of acylcarnitines as new candidate biomarkers for studies on the pathogenesis and development of HCC. Finally we discussed the challenges and perspectives of exploiting acylcarnitine metabolism and its related metabolic pathways as a target for HCC diagnosis and prognosis.

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Section: Detection Of Acylcarnitines In Biological Samplesmentioning

confidence: 99%

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

2019

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“…For example, widely variable quantitative results from flow-injection MS/MS acylcarnitine profiling have been documented using proficiency test samples (8,9), with analysis of identical samples yielding values differing from each other by 5-to 10-fold. Specific problems with dicarboxylic acylcarnitine analysis have also been reported (10). Although flow-injection MS/MS is suitable for screening programs that identify patients with possible diseases, limitations in quantitative accuracy and selectivity diminish the utility of this technique for confirmatory testing, which requires more rigorous techniques as described in these references (11)(12)(13).…”

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Selective, Accurate, and Precise Quantitation of Glutarylcarnitine in Human Urine from a Patient with Glutaric Acidemia Type I

Minkler

Stoll

Ingalls

et al. 2017

The Journal of Applied Laboratory Medicine

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Background: Although correctly used in expanded newborn screening programs to identify patients with possible diseases, flow-injection tandem mass spectrometry (MS/MS) acylcarnitine "profiles" are inadequate for standard clinical uses owing to their limited quantitative accuracy and lack of selectivity. We report the application of our selective, accurate, and precise method for quantification of acylcarnitines, applied to urine glutarylcarnitine from a patient with glutaric acidemia type I (GAI). Methods: A previously validated acylcarnitine ultra-HPLC-MS/MS method was used, with a focus on analysis of glutarylcarnitine. Calibrants and samples were isolated by solid-phase extraction and derivatized with pentafluorophenacyl trifluoromethanesulfonate. Acylcarnitine pentafluorophenacyl esters were eluted in 14-min chromatograms. Standardized calibrants and a 13-point, 200-fold concentration range calibration curve were used for accurate quantification of glutarylcarnitine. Quality control samples validated method accuracy and long-term analytic stability. Results: Quantification of glutarylcarnitine in urine from a patient with GAI is reported. Long-term analytical stability of the method over a 5-year period is shown. Conclusions: Our method for acylcarnitine quantification is shown to be selective, accurate, and precise; thus, we recommend it for confirmatory testing and monitoring of plasma and urine samples from patients with GAI. IMPACT STATEMENT This article describes the application of our validated ultra-HPLC (UHPLC)-tandem mass spectrometry (MS/MS) acylcarnitine method to the selective, quantitative analysis of glutarylcarnitine in human urine, as well as plasma and cerebrospinal fluid. Specifically, glutaric acidemia type I patients who are low excretors of the diagnostic markers glutaric acid and 3-hydroxy-glutaric acid have benefited from this technique. Our selective multidimensional UHPLC chromatographic system separates C5 dicarboxylic acylcarnitines (e.g., glutarylcarnitine, ethylmalonylcarnitine, and methylsuccinylcarnitine). Standardized calibrants and multiple-point calibration curves provide highly accurate quantification. These results are not available from flow-injection MS/MS "profiles."

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Selective and accurate C5 acylcarnitine quantitation by UHPLC–MS/MS: Distinguishing true isovaleric acidemia from pivalate derived interference

Minkler

Stoll

Ingalls

et al. 2017

Journal of Chromatography B

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Kinetic and molecular orbital analyses of dicarboxylic acylcarnitine methylesterification show that derivatization may affect the screening of newborns by tandem mass spectrometry

Cited by 5 publications

References 12 publications

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

Selective, Accurate, and Precise Quantitation of Glutarylcarnitine in Human Urine from a Patient with Glutaric Acidemia Type I

Selective and accurate C5 acylcarnitine quantitation by UHPLC–MS/MS: Distinguishing true isovaleric acidemia from pivalate derived interference

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