Selective, sensitive and fluorometric determination of urinary cytosine with 4-trifluoromethylbenzamidoxime and N,N-dimethylformamide

Clin Chim Acta. 2014 Feb 15:429:123-8. doi: 10.1016/j.cca.2013.11.027. Epub 2013 Dec 1.

Abstract

Background: Cytosine in urine is one of the biomarkers for the diagnosis of metabolic immunodeficiency. It has been mentioned that a high level of cytosine is found in urine of children having immunodeficiency. In this study, we have developed a fluorescence (fluorescence) derivatization reaction of cytosine using 4-trifluoromethylbenzamidoxime (4-TFMBAO) as a fluorogenic reagent.

Methods: In this reaction, cytosine was mixed with 4-TFMBAO, K3[Fe(CN)6], N,N-dimethylformamide (DMF) and KOH in an aqueous solution. The mixture was heated at 100°C for 20 min. The fluorescence intensity of the mixture was measured with a spectrofluorometer.

Results: Under the optimized reaction conditions, a strong fluorescence was produced only from cytosine amongst 62 compounds including structurally related bio-substances. The selectivity and sensitivity of this method were compared with a conventional fluorescence one using 2-bromoacetophenone that reacts with cytosine, adenine and their related substances. The present method was sufficiently selective toward cytosine, and approximately 50 times more sensitive than the conventional one.

Conclusions: Our method permitted the quantitative determination of cytosine in human urines without any pretreatment for a primary screening test of inborn disorder in pyrimidine metabolism with immunodeficiency, and indicated the lower detection limit of 0.1 μmol/l cytosine which gave 3 times greater fluorescence intensity than that observed for the reagent blank.

Keywords: 4-TFMBAO; 4-Trifluoromethylbenzamidoxime; 4-trifluoromethylbenzamidoxime; BAO; Cytosine; DMF; Fluorogenic reaction; Human urine; N,N-dimethylformamide; Selective quantification; benzamidoxime.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamidines / chemistry*
  • Cytosine / chemistry*
  • Cytosine / urine*
  • Dimethylformamide / chemistry*
  • Fluorometry / methods*
  • Humans
  • Hydrocarbons, Fluorinated / chemistry*
  • Indicators and Reagents / chemistry
  • Limit of Detection
  • Urinalysis / methods*

Substances

  • 4-trifluoromethylbenzamidoxime
  • Benzamidines
  • Hydrocarbons, Fluorinated
  • Indicators and Reagents
  • Dimethylformamide
  • Cytosine