Tandem mass spectrometry in the clinical chemistry laboratory

Dooley, Kent C.

doi:10.1016/s0009-9120(03)00105-x

Cited by 58 publications

(38 citation statements)

References 87 publications

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“…Today, the clinical laboratory demands those factors and also shortand long-term robustness. An analytical methodology cannot be exploited in the clinical domain if it is lacking robustness and requires labor-consuming sample preparation (14,15 ).…”

Section: Discussionmentioning

confidence: 99%

Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

et al. 2007

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Background:The expansion of newborn screening programs has increased the number of newborns diagnosed with inborn errors of metabolism in the presymptomatic phase, but it has also increased the number of costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we aimed to develop a rapid liquid chromatographytandem mass spectrometry (LC-MS/MS) method to identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots. Methods: We studied newborn screening spots from 250 healthy controls; 124 from infants with abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed patients. Whole blood was eluted from a 3.2-mm dried blood spot by a CH 3 CN/H 2 O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray without derivatization. Total analysis time was 5 min per sample. Results: The assays were linear up to 3300 nmol/L for both metabolites. Intra-and interassay imprecision data were 3.6%-8% and 3.1%-6%, respectively, for MMA

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Section: Discussionmentioning

confidence: 99%

Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

et al. 2007

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“…This technology has been coupled with gas chromatography (GC/MS) 1 and has been used with success for the identification and quantification of relatively small molecules (with molecular mass Ͻ1,000 Da). Such molecules could be highly informative in newborn screening programs (13), toxicological and forensic applications (14), for delineating various types of inborn errors of metabolism (15), for detecting doping of athletes (16), etc. Over the last 15 years, we have seen a resurgence of this technology for studying larger molecules such as nucleic acids and proteins.…”

Section: Mass Spectrometrymentioning

confidence: 99%

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Diamandis¹

2004

Molecular & Cellular Proteomics

188

249

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Serum proteomic profiling, by using surfaced-enhanced laser desorption/ionization-time-of-flight mass spectrometry, is one of the most promising new approaches for cancer diagnostics. Exceptional sensitivities and specificities have been reported for some cancer types such as prostate, ovarian, breast, and bladder cancers. These sensitivities/specificities are far superior to those obtained by using classical cancer biomarkers. In this review, I concentrate more on questions that cast doubt on the results reported and propose experiments to investigate these questions in detail, before the technique is used at the clinic. It is clear that the method needs to be externally and thoroughly validated before clinical implementation is warranted. Molecular & Cellular Proteomics 3:367-378, 2004.Our current efforts to combat cancer are not very successful. Despite the recent spectacular advances in molecular medicine, genomics, proteomics, and translational research, mortality rates for the most prevalent cancers have not been significantly reduced. Some of the best available options to combat cancer include primary prevention, earlier diagnosis, and improved therapeutic interventions. We are now witnessing the development of new drugs against cancer that are based on rational instead of empirical designs. There is hope that some of these drugs will prove to be more effective at the clinic than older generations of medicines. In terms of primary prevention, we do not as yet have at hand any robust strategies, because the mechanisms of cancer initiation and progression are still largely unknown.One of the best strategies to combat cancer now is by early diagnosis and administration of effective treatment (1). Another approach includes close monitoring of the cancer patient after initial treatment (usually surgery) to detect early relapse and then prescribe additional therapy. A third valuable approach would be the stratification of patients into subgroups that respond better to different types of treatment (individualized therapy). Medical imaging and serum or tissue biomarkers are valuable tools for monitoring these patients in order to optimize clinical outcomes.In this review, I will concentrate on mass spectrometry as a diagnostic and cancer biomarker discovery tool. Much has been published on this technology, and excellent reviews have already been prepared (2-12). My presentation will be biased toward underlining potential limitations that have not been adequately addressed in the already existing extensive literature. MASS SPECTROMETRYMass spectrometry has been used as a diagnostic tool in clinical laboratories for many decades. This technology has been coupled with gas chromatography (GC/MS) 1 and has been used with success for the identification and quantification of relatively small molecules (with molecular mass Ͻ1,000 Da). Such molecules could be highly informative in newborn screening programs (13), toxicological and forensic applications (14), for delineating various types of inborn errors of metabolism (15...

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“…, have increasingly been exploited by clinical chemistry laboratories for monitoring of drug and hormone levels in blood and urine specimens (179). Only recently have mass spectrometry methods been broadly applied to the identification of bacteria and other microorganisms in the clinical microbiology laboratory.…”

Section: Mass Spectrometry (Ms) Methods Including Gas Chromatographymentioning

confidence: 99%

“…Like MALDI-TOF MS, ESI-MS is a form of soft ionization which lends itself to analysis of larger macromolecules, including proteins and nucleic acids (179,180). In contrast to MALDI, ESI requires analytes to be dissolved in a liquid-phase carrier (aqueous or polar) for analysis ( Table 4).…”

Section: Electrospray Ionization Msmentioning

confidence: 99%

Emerging Technologies for the Clinical Microbiology Laboratory

2014

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SUMMARY In this review we examine the literature related to emerging technologies that will help to reshape the clinical microbiology laboratory. These topics include nucleic acid amplification tests such as isothermal and point-of-care molecular diagnostics, multiplexed panels for syndromic diagnosis, digital PCR, next-generation sequencing, and automation of molecular tests. We also review matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) and electrospray ionization (ESI) mass spectrometry methods and their role in identification of microorganisms. Lastly, we review the shift to liquid-based microbiology and the integration of partial and full laboratory automation that are beginning to impact the clinical microbiology laboratory.

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Tandem mass spectrometry in the clinical chemistry laboratory

Cited by 58 publications

References 87 publications

Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations

Emerging Technologies for the Clinical Microbiology Laboratory

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