Application of fast atom bombardment with tandem mass spectrometry and liquid chromatography/ mass spectrometry to the analysis of acylcarnitines in human urine, blood, and tissue

Millington, David S.; Norwood, Daniel L.; Kodo, Naoki; Roe, Charles R.; Inoue, Fumio

doi:10.1016/0003-2697(89)90441-7

Cited by 184 publications

(78 citation statements)

References 14 publications

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“…During the last 15 years mass spectrometry-based methods revolutionized approaches for diagnosing congenital metabolic disorders in newborns (Millington et al, 1989;Chace et al, 1993); current and future developments in mass spectrometry will likely have major impact on the diagnostic practices in endocrinology and other fields of medicine. Future applications of LC-MS in …”

Section: Discussionmentioning

confidence: 99%

“…Derivatization proved to be useful in the high-throughput screening of acylcarnitines (Millington et al, 1989), amino acids (Chace et al, 1993), and organic acids (Johnson, 1999); high-throughput quantitative analysis of methylmalonic acid (MMA) (Kushnir et al, 2001;Kushnir, Rockwood, & Nelson, 2004); to reduce the sample volume required for the analysis of endogenous steroids (Kushnir et al, 2006a(Kushnir et al, ,b, 2008; and in cases when very limited samples are available for analysis (Kushnir et al, 2009). …”

Section: Lc-ms/ms In Clinical Diagnosticsmentioning

confidence: 99%

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Liquid chromatography-tandem mass spectrometry applications in endocrinology

Kushnir

Rockwood

Bergquist

2009

Mass Spectrom. Rev.

138

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Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC-MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on-line and off-line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC-MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles. #

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Section: Discussionmentioning

confidence: 99%

Section: Lc-ms/ms In Clinical Diagnosticsmentioning

confidence: 99%

Liquid chromatography-tandem mass spectrometry applications in endocrinology

Kushnir

Rockwood

Bergquist

2009

Mass Spectrom. Rev.

138

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“…Millington and co-workers pioneered tandem mass spectrometry (MS/MS) methods for assaying carnitine and ACs in urine and plasma samples (5), and in dried blood spots (DBS). The development of electrospray ionization (ESI) has enabled the sample to be added to a continuously flowing solvent stream (flow injection analysis, FIA) and offers a more robust, more sensitive alternative to fast atom bombardment (FAB) MS/MS for AC profiling (6).…”

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confidence: 99%

Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns

et al. 2014

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Background: Acylcarnitines are biomarkers of fatty acid metabolism, and examining their patterns in preterm newborn may reveal metabolic changes associated with particular conditions related to prematurity. Isomeric acylcarnitines in dried blood spots (DBS) and plasma have never been assessed in preterm infants. Methods: We studied 157 newborn divided into four groups by weeks of gestational age (GA), as follows: 22-27 wk in group 1; 28-31 wk in group 2; 32-36 wk in group 3; and 37-42 wk in group 4. Samples were collected on the third day of life. Acylcarnitines were separated and quantified using ultra-performance liquid chromatography tandem mass spectrometry. results: Acylcarnitine concentrations correlated significantly with GA and birth weight in both DBS and plasma samples. Concentrations were lower in preterm newborn, except for acylcarnitines derived from branched-chain amino acids, which were higher and correlated with enteral feeding. On day 3 of life, no correlations emerged with gender, respiratory distress syndrome, bronchopulmonary dysplasia, surfactant administration, or mechanical ventilation. conclusion: We established GA-based reference ranges for isomeric acylcarnitine concentrations in preterm newborn, which could be used to assess nutritional status and the putative neuroprotective role of acylcarnitines.F atty acid metabolism takes place in the mitochondria, and β-oxidation is the main process by which fatty acids are oxidized by means of a sequential removal of two-carbon units from the acyl chain. Fatty acids are activated primarily in the cytosol by fatty acyl-CoA synthase to carnitine derivatives, then they are carried by specific acylcarnitine (AC) transferases and translocases into the mitochondrial matrix where β-oxidation can begin. In successive cycles of reactions, this process generates a series of ACs that are one two-carbon unit shorter and it continues until only two or three carbons are left (forming acetyl-CoA or propionyl-CoA, respectively). AC detection is of great interest for the purpose of assessing the carnitine pool, which is essential to the diagnosis of several metabolic disorders. AC profiling is a powerful tool for the neonatal screening and diagnosis of fatty acid oxidation and organic acid disorders (1). Alongside the importance of AC in tissues such as heart and muscle, recent data indicate an involvement of these compounds in neurological protection and disorders. ACs are believed to have both energy-providing and neuroprotective roles in the brain (2,3), based on the assumption that the fatty acid oxidation pathway is active in neurons, given the localization of carnitine palmitoyltransferase enzyme 1 (CPT1) (2,4). Investigating AC profiles in preterm infants may therefore reveal metabolic changes associated with perinatal brain injury.Mass spectrometry (MS) is commonly used to quantify ACs. Millington and co-workers pioneered tandem mass spectrometry (MS/MS) methods for assaying carnitine and ACs in urine and plasma samples (5), and in dried blood spots (DBS...

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“…Rapid increases in the number of known genetic and metabolic conditions and improved methodologies have led to expansion of candidate disorders for screening. Technological advances have been closely intertwined with the ability to screen for conditions, for example, the adaptation of tandem mass spectrometry (MS/MS) for detection and quantification of multiple analytes in newborns' blood spot samples (Millington et al 1989).…”

Section: N Ewborn Screening (Nbs) In the Unitedmentioning

confidence: 99%