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Clinical Chemistry 44: 2511-2515, 1998;
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(Clinical Chemistry. 1998;44:2511-2515.)
© 1998 American Association for Clinical Chemistry, Inc.

Drug Monitoring and Toxicology

Identification of 6-methylmercaptopurine derivative formed during acid hydrolysis of thiopurine nucleotides in erythrocytes, using liquid chromatography–mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance assay

Thierry Dervieux and Roselyne Boulieua

a Address correspondence to this author at: Université Claude Bernard Lyon 1, Institut des Sciences Pharmaceutiques et Biologiques, Département de Pharmacie Clinique, de Phamacocinétique et d'Evaluation du Médicament, 8 avenue Rockefeller, 69373 Lyon Cedex 08, France. Fax 04 78 77 71 58.

6-Thioguanine and 6-methylmercaptopurine (Me6-MP) nucleotides are the two major thiopurine metabolites of azathioprine found in erythrocytes. During the acid hydrolysis required for the conversion of thiopurine nucleotides into their free bases, Me6-MP was converted into a compound that could be analyzed on a Purospher RP18-e column with dihydrogen phosphate-methanol buffer as eluent. The pH of the acid extract strongly influenced the conversion of Me6-MP into its derivative. The Me6-MP derivative was identified using liquid chromatography–mass spectrometry and infrared and nuclear magnetic resonance spectrometric methods. During the acid hydrolysis of thiopurine nucleotides in erythrocytes, Me6-MP undergoes degradation, leading to 4-amino-5-(methylthio)carbonyl imidazole.




The following articles in journals at HighWire Press have cited this article:


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T. Dervieux, G. Meyer, R. Barham, M. Matsutani, M. Barry, R. Boulieu, B. Neri, and E. Seidman
Liquid Chromatography-Tandem Mass Spectrometry Analysis of Erythrocyte Thiopurine Nucleotides and Effect of Thiopurine Methyltransferase Gene Variants on These Metabolites in Patients Receiving Azathioprine/6-Mercaptopurine Therapy
Clin. Chem., November 1, 2005; 51(11): 2074 - 2084.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
T. Dervieux, Y. Chu, Y. Su, C.-H. Pui, W. E. Evans, and M. V. Relling
HPLC Determination of Thiopurine Nucleosides and Nucleotides in Vivo in Lymphoblasts following Mercaptopurine Therapy
Clin. Chem., January 1, 2002; 48(1): 61 - 68.
[Abstract] [Full Text] [PDF]


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