European Journal of Clinical Pharmacology

, Volume 62, Supplement 1, pp 51–59 | Cite as

Circulating and excretory nitrite and nitrate as indicators of nitric oxide synthesis in humans: methods of analysis

  • Dimitrios Tsikas
  • Frank-Mathias Gutzki
  • Dirk O. Stichtenoth
Review Article


Nitric oxide (NO) is produced in various cells from l-arginine by the catalytical action of NO synthases (NOS). The main metabolic fate of NO includes oxidation to nitrate by oxyhemoglobin in red blood cells and autoxidation to nitrite. Nitrate and nitrite circulate in blood and are excreted in urine. The concentration of these NO metabolites in plasma, serum, and urine can be used to assess NO synthesis in humans. Circulating nitrite reflects constitutive endothelial NOS activity. Excretory nitrate indicates systemic NO production. Nitrite and nitrate can be measured in plasma, serum, and urine of humans by various analytical methods which are based on different analytical principles. These methods include colorimetry, spectrophotometry, fluorescence, chemiluminescence, gas and liquid chromatography, electrophoresis, and mass spectrometry. The present article gives an overview of the most significant currently used quantitative methods of analysis of nitrite and nitrate in human plasma, serum, and urine in the framework of clinical studies and discusses their significance.


Nitric oxide Analysis Quality control 



The authors thank Prof. J. C. Frölich, the former Head and Director of the Institute of Clinical Pharmacology, for his invaluable support. The laboratory assistance of B. Beckmann, I. Fuchs, A. Mitschke and M.-T. Suchy is gratefully acknowledged.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Dimitrios Tsikas
    • 1
  • Frank-Mathias Gutzki
    • 1
  • Dirk O. Stichtenoth
    • 1
  1. 1.Institute of Clinical Pharmacology, Hannover Medical SchoolHannoverGermany

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