The analysis of diagnostic markers of genetic disorders in human blood and urine using tandem mass spectrometry with liquid secondary ion mass spectrometry

Millington, David S.; Kodo, Naoki; Terada, Naoto; Roe, Diane S.; Chace, Donald H.

doi:10.1016/0168-1176(91)85056-r

Cited by 125 publications

(77 citation statements)

References 15 publications

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“…The major loss observed is the loss of 75 Da, the neutral glycine moiety. No fragment ion at m/z 76 is generated because there is no available proton on carbon 2 of the acyl group [19,22]. An IDA method, which uses a survey scan of neutral loss of 75, should be used to detect acylgycines, including tiglyglycine, 3-methycrotonylglycine, hippuric acid, and hydroxyhippuric acid isomers, among others.…”

Section: Ms Fragmentation Patterns Of Standardsmentioning

confidence: 99%

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A method for comprehensive analysis of urinary acylglycines by using ultra-performance liquid chromatography quadrupole linear ion trap mass spectrometry

Lewis-Stanislaus

Liang

2010

J. Am. Soc. Mass Spectrom.

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Acylglycines are an important class of metabolites that have been used in the diagnosis of several inborn errors of metabolism (IEM). However, current analytical methods detect only a few acylglycines. There is a need to profile these metabolites in a comprehensive manner for studying their functions and improving their diagnostic values for different IEM and potentially other diseases. We describe a sensitive method that combines the chromatographic resolving power of ultra-performance liquid chromatography (UPLC) to separate closely related metabolites including isomers with tandem mass spectrometry (MS/MS). Acylglycines were extracted from urine using an anion exchange solid-phase extraction (SPE) cartridge. After UPLC separation, the acylglycines were detected on a hybrid triple quadrupole linear ion trap mass spectrometer. A set of standards were used for the development of an optimal MS acquisition method. Several acquisition modes using information derived from collisioninduced dissociation breakdown curves were used to detect acylglycines. Using this method, 18 acylglycines were detected in the urine of healthy individuals and confirmed using standards, while 47 additional acylglycines were detected and tentatively identified, based on their retention and fragmentation pattern. Among the 65 acylglycines detected, only 18 of them have been previously reported in biofluids of healthy individuals. These results will be deposited in a public human metabolome database. This example illustrates that by developing a method tailored to the analysis of a class of metabolites sharing similar structural moieties, we can potentially identify many more new metabolites, thereby expanding the overall metabolome coverage. (J Am Soc Mass Spectrom 2010, 21, 2105-2116) © 2010 American Society for Mass Spectrometry M etabolomics is an emerging field that is poised to play a significant role in many disciplines of biosciences. One of the current challenges in metabolomics is to profile the metabolome in a very comprehensive manner, ideally covering the entire set of metabolites present in a biological system. However, due to technical limitations, only a small portion of the metabolome is analyzed. There is a great need to expand the metabolome coverage to reveal subtle changes of the metabolome in biological studies or disease biomarker discovery. Liquid chromatography mass spectrometry (LC/MS) is a sensitive technique that can detect many metabolites in a metabolome sample [1]. However, metabolite identification from the mass spectral data alone is often difficult [2][3][4][5][6]. There are only a limited number of metabolite standards available for spectral comparison to identify unknowns. For example, in the Human Metabolome Database (HMDB), product ion spectra of about 900 known standards obtained by tandem mass spectrometry (MS/MS) are included. To create this MS/MS spectral library, we went through almost all the possible commercial sources to acquire the available metabolite standards [7]. This number is still quite ...

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Section: Ms Fragmentation Patterns Of Standardsmentioning

confidence: 99%

“…This fragmentation pathway occurs because aliphatic acylglycines lose the acyl moiety as a ketene. There must be an available proton on carbon 2 of the acyl group in order for this fragmentation to occur [19].…”

Section: Ms Fragmentation Patterns Of Standardsmentioning

confidence: 99%

A method for comprehensive analysis of urinary acylglycines by using ultra-performance liquid chromatography quadrupole linear ion trap mass spectrometry

Lewis-Stanislaus

Liang

2010

J. Am. Soc. Mass Spectrom.

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“…Early publications using FAB or FIB ionization demonstrated that this process facilitated ionization and improved sensitivity (45,64 ). As ionization methods improved, e.g., through advances in electrospray ionization, underivatized samples could also be analyzed for many acylcarnitines and amino acids (see Figs.…”

Section: Preparation For Ms/ms Analysismentioning

confidence: 99%

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Chace¹,

Kalas²,

Naylor³

2003

Clinical Chemistry

569

366

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Background: Over the past decade laboratories that test for metabolic disorders have introduced tandem mass spectrometry (MS/MS), which is more sensitive, specific, reliable, and comprehensive than traditional assays, into their newborn-screening programs. MS/MS is rapidly replacing these one-analysis, one-metabolite, one-disease classic screening techniques with a oneanalysis, many-metabolites, many-diseases approach that also facilitates the ability to add new disorders to existing newborn-screening panels. Methods: During the past few years experts have authored many valuable articles describing various approaches to newborn metabolic screening by MS/MS. We attempted to document key developments in the introduction and validation of MS/MS screening for metabolic disorders. Our approach used the perspective of the metabolite and which diseases may be present from its detection rather than a more traditional approach of describing a disease and noting which metabolites are increased when it is present. Content: This review cites important historical developments in the introduction and validation of MS/MS screening for metabolic disorders. It also offers a basic technical understanding of MS/MS as it is applied to multianalyte metabolic screening and explains why MS/MS is well suited for analysis of amino acids and acylcarnitines in dried filter-paper blood specimens. It also describes amino acids and acylcarnitines as they are detected and measured by MS/MS and their significance to the identification of specific amino acid, fatty acid, and organic acid disorders. Conclusions: Multianalyte technologies such as MS/MS are suitable for newborn screening and other mass

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“…In a first stage, methyl esterification was used previously for analysis of acylcarnitines in plasma [23] but later on the most part of laboratories switched off to butylation.…”

Section: Analysis By Msmentioning

confidence: 99%

Mass spectrometry in clinical chemistry: the case of newborn screening

Marca

2014

Journal of Pharmaceutical and Biomedical Analysis

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Keywords:Newborn screening LC-MS/MS Tandem mass spectrometry Inborn errors of metabolism Clinical chemistry a b s t r a c t Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods.Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system.

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The analysis of diagnostic markers of genetic disorders in human blood and urine using tandem mass spectrometry with liquid secondary ion mass spectrometry

Cited by 125 publications

References 15 publications

A method for comprehensive analysis of urinary acylglycines by using ultra-performance liquid chromatography quadrupole linear ion trap mass spectrometry

A method for comprehensive analysis of urinary acylglycines by using ultra-performance liquid chromatography quadrupole linear ion trap mass spectrometry

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

Mass spectrometry in clinical chemistry: the case of newborn screening

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