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Drug Monitoring and Toxicology |
1
Institut des Sciences Pharmaceutiques et Biologiques, Université Claude Bernard, Lyon I, Laboratoire de Pharmacie Clinique, 8 ave. Rockefeller, 69373 Lyon Cedex 08, France.
2
Hôpital Cardiovasculaire et Pneumologique, Service
Pharmaceutique, B.P. Lyon-Montchat, 69394 Lyon Cedex 03, France.
a Address correspondence to this author at the first address. Fax 04.78.77.7158.
6-thioguanine (6-TGN) and methyl 6-mercaptopurine nucleotides (Me6-MPNs) are the two major metabolites found in erythrocytes after administration of azathioprine. In an attempt to understand the role of these metabolites in the pharmacologic and toxic activity of thiopurines, we have developed a HPLC method for the simultaneous determination of 6-TGNs and Me6-MPNs in erythrocytes. A simple and rapid treatment procedure based on deproteinization by perchloric acid with dithiothreitol is described. The nucleotides were hydrolyzed to their own bases by heating the sample for 45 min at 100 °C. During acid hydrolysis Me6-MP was converted into a compound analyzed on a Purospher RP18-e column with 0.02 mol/L dihydrogenophosphate buffer–methanol as eluents. With this procedure, mean recoveries of 73.1% and 84.0% for 6-TGN and Me6-MPN derivatives, respectively, were found
The following articles in journals at HighWire Press have cited this article:
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  R. A. el-Azhary, S. A. Farmer, L. A. Drage, R. S. Rogers III, M. T. McEvoy, M. D. P. Davis, A. G. Bridges, and L. E. Gibson Thioguanine Nucleotides and Thiopurine Methyltransferase in Immunobullous Diseases: Optimal Levels as Adjunctive Tools for Azathioprine Monitoring Arch Dermatol, June 1, 2009; 145(6): 644 - 652. [Abstract] [Full Text] [PDF]
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 M. Reinshagen, E. Schutz, V. W. Armstrong, C. Behrens, C. von Tirpitz, A. Stallmach, H. Herfarth, J. Stein, P. Bias, G. Adler, et al. 6-Thioguanine Nucleotide-Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial Clin. Chem., July 1, 2007; 53(7): 1306 - 1314. [Abstract] [Full Text] [PDF]
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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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 B M de Oliveira, M B Viana, C L Zani, and A J Romanha Clinical and laboratory evaluation of compliance in acute lymphoblastic leukaemia Arch. Dis. Child., August 1, 2004; 89(8): 785 - 788. [Abstract] [Full Text] [PDF]
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L. Lennard, M. Shipkova, V. W. Armstrong, E. Wieland, and M. Oellerich Commentary on: Differences in Nucleotide Hydrolysis Contribute to the Differences between Erythrocyte 6-Thioguanine Nucleotide Concentrations Determined by Two Widely Used Methods * The authors of the article cited above respond: Clin. Chem., September 1, 2003; 49(9): 1551 - 1552. [Full Text] [PDF]
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 S. Gunnarsdottir and A. A. Elfarra DISTINCT TISSUE DISTRIBUTION OF METABOLITES OF THE NOVEL GLUTATHIONE-ACTIVATED THIOPURINE PRODRUGS CIS-6-(2-ACETYLVINYLTHIO)PURINE AND TRANS-6-(2-ACETYLVINYLTHIO)GUANINE AND 6-THIOGUANINE IN THE MOUSE Drug Metab. Dispos., June 1, 2003; 31(6): 718 - 726. [Abstract] [Full Text] [PDF]
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M. Shipkova, V. W. Armstrong, E. Wieland, and M. Oellerich Differences in Nucleotide Hydrolysis Contribute to the Differences between Erythrocyte 6-Thioguanine Nucleotide Concentrations Determined by Two Widely Used Methods Clin. Chem., February 1, 2003; 49(2): 260 - 268. [Abstract] [Full Text] [PDF]
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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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 T. Dervieux, J. G. Blanco, E. Y. Krynetski, E. F. Vanin, M. F. Roussel, and M. V. Relling Differing Contribution of Thiopurine Methyltransferase to Mercaptopurine versus Thioguanine Effects in Human Leukemic Cells Cancer Res., August 1, 2001; 61(15): 5810 - 5816. [Abstract] [Full Text] [PDF]
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R. Boulieu, M. Sauviat, T. Dervieux, M. Bertocchi, and J.-F. Mornex Phenotype Determination of Thiopurine Methyltransferase in Erythrocytes by HPLC Clin. Chem., May 1, 2001; 47(5): 956 - 958. [Full Text] [PDF]
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T. Dervieux and R. Boulieu 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 Clin. Chem., December 1, 1998; 44(12): 2511 - 2515. [Abstract] [Full Text] [PDF]
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