Journal of Inherited Metabolic Disease

, Volume 28, Issue 6, pp 951–963 | Cite as

Analysis of polyols in urine by liquid chromatography–tandem mass spectrometry: A useful tool for recognition of inborn errors affecting polyol metabolism

  • M. M. C. Wamelink
  • D. E. C. Smith
  • C. Jakobs
  • N. M. Verhoeven


Several inborn errors of metabolism with abnormal polyol concentrations in body fluids are known to date. Most of these defects can be diagnosed by the assessment of urinary concentrations of polyols. We present two methods using tandem mass spectrometry for screening for inborn errors affecting polyol metabolism. Urine samples supplemented with internal standards ([13C4]erythritol, [13C2]arabitol and [2H3]sorbitol) were desalted by a mixed-bed ion-exchange resin. Separation was achieved by two different columns. Sugar isomers could not be separated using a Prevail Carbohydrate ES 54 column (method 1), whereas with the other column (Aminex HPX-87C) separation of the isomers was achieved (method 2). Multiple reaction monitoring polyol detection was achieved by tandem mass spectrometry with an electron ion-spray source operating in the negative mode. Age-related reference ranges of polyols (erythritol, treitol, arabitol, ribitol, xylitol, galactitol, mannitol, sorbitol, sedoheptitol and perseitol) in urine were established. The applicability of the method was demonstrated by the abnormal polyol concentrations observed in patients with transaldolase deficiency, ribose-5-phosphate isomerase deficiency and classical galactosaemia. This paper describes two methods for the analysis of urinary polyols by liquid chromatography–tandem mass spectrometry. Method 1 is a fast screening method with the quantification of total isomers and method 2 is a more selective method with the separate quantification of the polyols. Both methods can be used for diagnosing inborn errors of metabolism affecting polyol metabolism.


Tandem Mass Spectrometry Polyol Xylitol Inborn Error Erythritol 
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  1. Bosch AM, Bakker HD, Maillette de Buy Wenniger-Prick LJ, Wanders RJA, Wijburg FA (2004) High tolerance for oral galactose in classical galactosemia: dietary implications. Arch Dis Child 89: 1034–1036.CrossRefPubMedGoogle Scholar
  2. Endres W, Shin YS (1990) Cataract and metabolic disease. J Inherit Metab Dis 13: 509–516.PubMedGoogle Scholar
  3. Haga H, Nakajima T (1989) Determination of polyol profiles in human urine by capillary gas chromatography. Biomed Chromatogr 3: 68–71.CrossRefPubMedGoogle Scholar
  4. Huck HJ, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS (2004) Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Am J Hum Genet 74: 745–751.CrossRefPubMedGoogle Scholar
  5. Jandera P, Churácek J (1974) Ion-exchange chromatography of nitrogen compounds. J Chromatogr 98: 1–54.PubMedGoogle Scholar
  6. Jansen G, Muskiet FA, Schierbeek H, Berger R, van der Slik SW (1986) Capillary gas chromatographic profiling of urinary, plasma and erythrocyte sugars and polyols as their trimethylsilyl derivatives, preceded by a simple and rapid prepurification method. Clin Chim Acta 157: 277–293.CrossRefPubMedGoogle Scholar
  7. Karabinos JV, Ballun AT (1953) Direct reduction of aldoses and ketoses by Raney nickel. J Amer Chem Soc 75: 4501–4502.Google Scholar
  8. Lane AB (1985) On the nature of L-xylulose reductase deficiency in essential pentosuria. Biochem Genet 23: 61–72.CrossRefPubMedGoogle Scholar
  9. Lee AY, Chung SS (1999) Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 13: 23–30.Google Scholar
  10. Onkenhout W, Groener JE, Verhoeven NM, Yin C, Laan LA (2002) L-Arabinosuria: a new defect in human pentose metabolism. Mol Genet Metab 77: 80–85.CrossRefPubMedGoogle Scholar
  11. Passing H, Bablok W (1983) A new biometrical procedure for testing the equality of measurements from two different analytical methods. Application of linear regression procedures for method comparison studies in clinical chemistry, Part I. J Clin Chem Clin Biochem 21: 709–720.PubMedGoogle Scholar
  12. Tetsuo M, Zhang C, Matsumoto H, Matsumoto I (1999) Gas chromatography–mass spectrometric analysis of urinary sugar and sugar alcohols during pregnancy. J Chromatogr B 731: 111–120.Google Scholar
  13. Verhoeven NM, Huck JH, Roos B, et al (2001) Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway. Am J Hum Genet 68: 1086–1092.CrossRefPubMedGoogle Scholar
  14. Verhoeven NM, Wallot M, Huck JHJ, et al (2005) A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency. J Inherit Metab Dis 2: 169–179.Google Scholar

Copyright information

© SSIEM and Springer 2005

Authors and Affiliations

  • M. M. C. Wamelink
    • 1
  • D. E. C. Smith
    • 1
  • C. Jakobs
    • 1
  • N. M. Verhoeven
    • 1
    • 2
  1. 1.Department of Clinical Chemistry, Metabolic UnitVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Metabolic Unit, Department of Clinical ChemistryVU University Medical CenterHV AmsterdamThe Netherlands

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