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Abstract

Tandem mass spectrometry (MS/MS) is an analytical method that uses two mass analyzers to perform the separation and analysis of mixture components after ionizing them, usually by means of a “soft” ionization technique such as electrospray or fast ion bombardment. The method differs from the more familiar gas chromatography/mass spectrometry (GC/MS) method, used primarily for analysis of organic acids in urine, in several ways. MS/ MS is applicable to polar compounds that are not readily amenable to GC/ MS. By limiting or altogether avoiding the chromatography step, the analytical process is much faster and therefore capable of high specimen throughput. MS/MS is well suited to the quantitative analysis of specific metabolites or to groups of metabolites having similar chemical structure. It is thus a useful adjunct to GC/MS and other methods currently used in clinical diagnostic laboratories. Clinical applications of MS/MS are almost exclusively performed on a “triple” quadrupole mass spectrometer [1], equipped with electro spray ionization [2] and an automated sample introduction system. The central quadrupole in this type of instrument is actually a device that induces fragmentation and not a mass analyzer.

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References

  1. Yost RA, Enke C.G. Tandem Quadrupole Mass Spectrometry. In: McLafferty FW, editor. Tandem Mass Spectrometry. New York: Wiley; 1983. p. 175–95.

    Google Scholar 

  2. Electrospray Ionization Mass Spectrometry. Cole RB, editor. New York: John Wiley & Sons, Inc; 1997.

    Google Scholar 

  3. Millington DS, Chace DH. Carnitine and Acylcarnitines in Metabolic Disease Diagnos and Management. In: Desiderio DM, editor. Mass Spectrometry: Clinical and Biomedical Applications. Volume 1. New York: Plenum Press; 1992. p. 199–219.

    Google Scholar 

  4. Chace DH, Millington DS, Terada N, Kahler SG, Roe CR, Hofman LH. Rapid Diagnosis of Phenylketonuria by Quantitative Analysis of Phenylalanine and Tyrosine in Neonatal Blood Spots Using Tandem Mass Spectrometry. Clin. Chem. 1993;39:66–71.

    PubMed  CAS  Google Scholar 

  5. Chace DH, Hillman SL, Millington DS, Kahler SG, Adam BW, Levy HL. Rapid Diagnosis of Homocystinuria and other Hypermethioninemias from Newborns’ Blood Spots by Tandem Mass Spectrometry. Clin. Chem. 1996;42:349–55.

    PubMed  CAS  Google Scholar 

  6. Magera MJ, Lacey JM, Casetta B, Rinaldo P. Method for the determination of total homocysteine in plasma and urine by stable isotope dilution and electro spray tandem mass spectrometry. Clin. Chem. 1999;45(9):1517–22.

    PubMed  CAS  Google Scholar 

  7. Ito T, van Kuilenburg AB, Bootsma AH, Haasnoot AJ, van Cruchten A, Wada Y et al. Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urinesoaked filter paper strips. Clin. Chem. 2000;46(4):445–52.

    PubMed  CAS  Google Scholar 

  8. Bonafe L, Troxler H, Kuster T, Heizmann CW, Chamoles NA, Burlina AB et al. Evaluation of urinary acylglycines by electro spray tandem mass spectrometry in mitochondrial energy metabolism defects and organic acidurias. Mol. Genet. Metab. 2000;69(4):302–11.

    Article  PubMed  CAS  Google Scholar 

  9. Mills KA, Mushtaq I, Johnson AW, Whitfield PD, Clayton PT. A method for the quantitation of conjugated bile acids in dried blood spots using electrospray-ionization mass spectrometry. Pediatr. Res. 1998;43(3):361–8.

    Article  PubMed  CAS  Google Scholar 

  10. Bootsma AH, Overmars H, van Rooj A, van Lint AE, Wanders RJ, van Gennip AH, et al. Rapid analysis of conjugated bile acids in plasma using electrospray tandem mass spectrometry: application for selective screening of peroxisomal disorders. J. Inher. Metab. Dis. 1999;22(3):307–10

    Article  PubMed  CAS  Google Scholar 

  11. Vreken P, Valianpour F, Overmars H, Barth PG, Selhorst JJ, van Gennip AH, Wanders RJ. Analysis of plasmenylethanolamines using electrospray tandem mass spectrometry and its application in screening for peroxisomal disorders. J. Inher. Metab. Dis. 2000;23(4):429–33.

    Article  PubMed  CAS  Google Scholar 

  12. Nada MA, Chace DH, Sprecher H, Roe CR. Investigation of beta-oxidation intermediates in normal and MCAD-deficient human fibroblasts using tandem mass spectrometry. Biochem. Mol. Med. 1995;54(1):59–66.

    Article  PubMed  CAS  Google Scholar 

  13. Roe CR, Roe DS. Detection of gene defects in branched-chain amino acid metabolism by tandem mass spectrometry of carnitine esters produced by cultured fibroblasts. Methods Enzymol. 2000;324:424–31.

    Article  PubMed  CAS  Google Scholar 

  14. Rashed MS, Bucknall MP, Little D, Awad A, Jacob M, Alamoudi M et al. Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batched process and a computer algorithm for automated flagging of abnormal profiles. Clin. Chem. 1997;43(7):1129–41

    PubMed  CAS  Google Scholar 

  15. Abdenur JE, Chamoles NA, Guinle AE, Schenone AB, Fuertes AN. Diagnosis of isovaleric acidaemia by tandem mass spectrometry: false positive result due to pivaloylcarnitine in a newborn screening programme. J. Inherit. Metab. Dis. 1998;21(6):624–30.

    Article  PubMed  CAS  Google Scholar 

  16. Costa CC, De Almeida IT, Jakobs C, Poll-The BT, Duran M. Dynamic changes of plasma acylcarnitine levels induced by fasting and sunflower oil challenge test in children. Pediatr. Res. 1999;46(4):440–4.

    Article  PubMed  CAS  Google Scholar 

  17. Stevens RD, Hillman SL, Worthy LS, Sanders D, Millington DS. Assay for Free and Total Carnitine in Human Plasma using Tandem Mass Spectrometry. Clin. Chem. 2000;46:727–9.

    PubMed  CAS  Google Scholar 

  18. Schmidt-Sommerfeld E, Werner D, Penn D. Carnitine plasma concentrations in 353 metabolically healthy children. Eur. J. Pediatr. 1988;147(4):356–60.

    Article  PubMed  CAS  Google Scholar 

  19. Van Hove JLK, Zhang W, Kahler SG, Roe CR, Chen Y-T, Terada N et al. MediumChain Acyl-CoA Dehydrogenase Deficiency: Diagnosis by Acylcarnitine Analysis in Blood. Am. J. Human Genet. 1993;52:958–66.

    Google Scholar 

  20. Millington DS, Kodo N, Norwood DL, Roe CR. Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J. Inher. Metab. Dis. 1990;13:321–4.

    Article  PubMed  CAS  Google Scholar 

  21. Naylor EW, Chace DH. Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol. 1999;14 Suppl 1:S4–8.

    PubMed  Google Scholar 

  22. Wiley V, Carpenter K, Wilken B. Newborn screening with tandem mass spectrometry: 12 months’ experience in NSW Australia. Acta. Paediatr. Suppl. 1999;88(432):48–51.

    Article  PubMed  CAS  Google Scholar 

  23. Millington DS, Kodo N, Terada N, Roe CR, Chace DH. The analysis of diagnostic markers of genetic disorders in human blood and urine using tandem mass spectrometry with liquid secondary ion mass spectrometry. Int. J. Mass Spectrom. Ion Processes 1991;111:211–228.

    Article  CAS  Google Scholar 

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Millington, D.S. (2003). Tandem Mass Spectrometry in Clinical Diagnosis. In: Blau, N., Duran, M., Blaskovics, M.E., Gibson, K.M. (eds) Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55878-8_5

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  • DOI: https://doi.org/10.1007/978-3-642-55878-8_5

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