{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:06:58Z","timestamp":1791313618500,"version":"4.3.1"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP) are used extensively in pediatric and adult patients with inflammatory and neoplastic diseases. They are metabolized to 6-thioguanine nucleotides (6-TGN) or to 6-methyl-mercaptopurine nucleotides (6-MMPN). The balance between 6-TGN and 6-MMPN is highly variable and monitoring is recommended, but its benefit in outcome gives rise to conflicting results, potentially increased by differences in quantifying 6-MP metabolism. Our aim was to report (1) the HPLC-UV procedure used in our laboratory to quantify red blood cells (RBCs) with 6-TGN and 6-MMPN (as its derivate: 6-MMP(d)) in patients treated with thiopurines and (2) additional tests, sometimes confirmatory, to improve method standardization. The comparison of two methods to count RBCs shows that metabolite concentrations were slightly lower in the washed and resuspended RBCs than in whole blood. Perchloric acid (0.7 M), dithiothreitol (DTT, final 0.013 M sample concentration) and 60 min hydrolysis were selected for acid hydrolysis. (3) Monitoring data from 83 patients receiving AZA or 6-MP showed that at steady state, only 53\/183 (29%) had 6-TGN and 6-MMPN in the recommended therapeutic range. Our method is discussed in light of the technical conditions and sample stability data from 17 publications identified since the first analytical report in 1987. Monitoring data demonstrate, if required, that inter-patient variability in 6-TGN and 6-MMPN concentrations is high in samples from treated patients.<\/jats:p>","DOI":"10.3390\/ijms231911885","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Improved HPLC Quantification of 6-Mercaptopurine Metabolites in Red Blood Cells: Monitoring Data and Literature Analysis"],"prefix":"10.3390","volume":"23","author":[{"given":"Tiphaine","family":"Adam de Beaumais","sequence":"first","affiliation":[{"name":"Department of Biological Pharmacology and Pharmacogenetics, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Medard","sequence":"additional","affiliation":[{"name":"Department of Biological Pharmacology and Pharmacogenetics, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oc\u00e9ane","family":"Amblard","sequence":"additional","affiliation":[{"name":"Department of Biological Pharmacology and Pharmacogenetics, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauriane","family":"Goldwirt","sequence":"additional","affiliation":[{"name":"Department of Biological Pharmacology and Pharmacogenetics, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Simonin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, H\u00f4pital Armand Trousseau, Assistance Publique\u2014H\u00f4pitaux de Paris, 26 Avenue du Docteur Arnold Netter, 75012 Paris, France"},{"name":"Department of Education and Training, Sorbonne Universit\u00e9, 1 rue Victor Cousin, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Martinez Vinson","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition, H\u00f4pital Robert Debr\u00e9, Assistance Publique\u2014H\u00f4pitaux de Paris, 48 Boulevard Serurier, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8363-1622","authenticated-orcid":false,"given":"Arnaud","family":"Petit","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, H\u00f4pital Armand Trousseau, Assistance Publique\u2014H\u00f4pitaux de Paris, 26 Avenue du Docteur Arnold Netter, 75012 Paris, France"},{"name":"Department of Education and Training, Sorbonne Universit\u00e9, 1 rue Victor Cousin, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Jacqz-Aigrain","sequence":"additional","affiliation":[{"name":"Department of Biological Pharmacology and Pharmacogenetics, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 1 rue Charles Vellefaux, 75011 Paris, France"},{"name":"Department of Education and Training, Universit\u00e9 de Paris, 2 rue Albert Einstein, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.dld.2004.09.029","article-title":"Thiopurines in inflammatory bowel disease: Pharmacogenetics, therapeutic drug monitoring and clinical recommendations","volume":"37","author":"Derijks","year":"2005","journal-title":"Dig. Liver Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/00007691-200406000-00016","article-title":"Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease: Implications for therapy","volume":"26","author":"Derijks","year":"2004","journal-title":"Ther. Drug Monit."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/01.ftd.0000179839.71138.6d","article-title":"Pharmacokinetics of 6-thioguanine in patients with inflammatory bowel disease","volume":"28","author":"Derijks","year":"2006","journal-title":"Ther. Drug Monit."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/1751-2980.12536","article-title":"Critical assessment of thioguanine treatment for inflammatory bowel diseases: Is it time to rehabilitate this treatment?","volume":"18","author":"Movva","year":"2017","journal-title":"J. Digest. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1126\/science.2649979","article-title":"The purine path to chemotherapy","volume":"244","author":"Elion","year":"1989","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/BF02897232","article-title":"6-Thioguanine nucleotide accumulation in red blood cells during maintenance chemotherapy for childhood acute lymphoblastic leukemia, and its relation to leukopenia","volume":"26","author":"Schmiegelow","year":"1990","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_7","first-page":"1226","article-title":"Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: Results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988\u20131991)","volume":"94","author":"Kamps","year":"1999","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/pbc.20089","article-title":"A comparison of red blood cell thiopurine metabolites in children with acute lymphoblastic leukemia who received oral mercaptopurine twice daily or once daily: A Pediatric Oncology Group study (now The Children\u2019s Oncology Group)","volume":"43","author":"Bell","year":"2004","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/bjh.13469","article-title":"Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003","volume":"170","author":"Lennard","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1182\/blood.2021012328","article-title":"Remission, treatment failure, and relapse in pediatric ALL: An international consensus of the Ponte-di-Legno Consortium","volume":"139","author":"Buchmann","year":"2021","journal-title":"Blood"},{"key":"ref_11","first-page":"1197","article-title":"Immunosuppressive effects of specific classes of agents with special reference to organ transplantation. Immunosuppression by thiopurines","volume":"5","author":"Zweiman","year":"1973","journal-title":"Transplant. Proc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.3324\/haematol.2020.278166","article-title":"ncrements in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia","volume":"106","author":"Larsen","year":"2021","journal-title":"Haematologica"},{"key":"ref_13","first-page":"5810","article-title":"Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells","volume":"61","author":"Dervieux","year":"2001","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1097\/FTD.0000000000000326","article-title":"Rac1 as a Potential Pharmacodynamic Biomarker for Thiopurine Therapy in Inflammatory Bowel Disease","volume":"38","author":"Seinen","year":"2016","journal-title":"Ther. Drug Monit."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.3748\/wjg.v20.i13.3534","article-title":"Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?","volume":"20","author":"Stocco","year":"2014","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/03602538508991433","article-title":"The pharmacology and metabolism of the thiopurine drugs 6-mercaptopurine and azathioprine","volume":"16","author":"Johnson","year":"1985","journal-title":"Drug Metab. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/00043426-199302000-00010","article-title":"Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia","volume":"15","author":"Bostrom","year":"1993","journal-title":"Am. J. Pediatr. Hematol. Oncol."},{"key":"ref_18","first-page":"651","article-title":"Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity","volume":"32","author":"Weinshilboum","year":"1980","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","first-page":"143","article-title":"Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders: Influence on treatment response","volume":"10","author":"Abaji","year":"2017","journal-title":"Pharm. Pers. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/clpt.2008.154","article-title":"Genetic Polymorphism of Inosine Triphosphate Pyrophosphatase Is a Determinant of Mercaptopurine Metabolism and Toxicity During Treatment for Acute Lymphoblastic Leukemia","volume":"85","author":"Stocco","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/ng.3508","article-title":"NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity","volume":"48","author":"Moriyama","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1365-2125.1997.tb00148.x","article-title":"lntracellular thiopurine nucleotides and azathioprine myelotoxicity in organ transplant patients","volume":"43","author":"Boulieu","year":"1997","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nrc1800","article-title":"Acute lymphoblastic leukaemia: A model for the pharmacogenomics of cancer therapy","volume":"6","author":"Cheok","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1365-2125.2010.03867.x","article-title":"Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy","volume":"71","author":"Fakhoury","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2217\/pgs-2020-0095","article-title":"Pharmacogenetics of inflammatory bowel disease","volume":"22","author":"Coenen","year":"2021","journal-title":"Pharmacogenomics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1053\/j.seminhematol.2020.10.001","article-title":"Pharmacogenomics and ALL treatment: How to optimize therapy","volume":"57","author":"Karol","year":"2020","journal-title":"Semin. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0378-4347(87)80340-7","article-title":"Assay of 6-thioinosinic acid and 6-thioguanine nucleotides, active metabolites of 6-mercaptopurine, in human red blood cells","volume":"423","author":"Lennard","year":"1987","journal-title":"J. Chromatogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/clinchem\/44.3.551","article-title":"Simultaneous determination of 6-thioguanine and methyl 6-mercaptopurine nucleotides of azathioprine in red blood cells by HPLC","volume":"44","author":"Dervieux","year":"1998","journal-title":"Clin. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0378-4347(99)00195-4","article-title":"High-performance liquid chromotographic determination of methyl 6-mercaptopurine nucleotides (Me6-MPN) in red blood cells: Analysis of Me6-MPN per se or Me6-MPN derivative?","volume":"730","author":"Boulieu","year":"1999","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/FTD.0000000000000455","article-title":"Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients with Inflammatory Bowel Disease","volume":"39","author":"Simsek","year":"2017","journal-title":"Ther. Drug Monit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0021-9258(19)77771-0","article-title":"Antagonists of nucleic acid derivatives. VI. Purines","volume":"192","author":"Elion","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0016-5085(00)70140-5","article-title":"Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease","volume":"118","author":"Dubinsky","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1097\/01.ftd.0000169061.52715.3e","article-title":"Thiopurine therapies: Problems, complexities, and progress with monitoring thioguanine nucleotides","volume":"27","author":"Duley","year":"2005","journal-title":"Ther. Drug Monit."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1373\/clinchem.2007.086215","article-title":"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","volume":"53","author":"Reinshagen","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1097\/MIB.0000000000001168","article-title":"Optimizing Thiopurine Therapy in Inflammatory Bowel Disease Among 2 Real-life Intercept Cohorts: Effect of Allopurinol Comedication?","volume":"23","author":"Meijer","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/00007691-199706000-00013","article-title":"Possibilities for therapeutic drug monitoring of azathioprine: 6-thioguanine nucleotide concentrations and thiopurine methyltransferase activity in red blood cells","volume":"19","author":"Bergan","year":"1997","journal-title":"Ther. Drug Monit."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1139\/y96-056","article-title":"Quantitation of 6-thioguanine in peripheral blood leukocyte DNA in Crohn\u2019s disease patients on maintenance 6-mercaptopurine therapy","volume":"74","author":"Cuffari","year":"1996","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-4347(00)00513-2","article-title":"Improved methods for determining the concentration of 6-thioguanine nucleotides and 6-methylmercaptopurine nucleotides in blood","volume":"757","author":"Pike","year":"2001","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/00007691-200404000-00024","article-title":"Analytic aspects of monitoring therapy with thiopurine medications","volume":"26","author":"Armstrong","year":"2004","journal-title":"Ther. Drug Monit."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1515\/cclm-2018-0116","article-title":"A design for external quality assessment for the analysis of thiopurine drugs: Pitfalls and opportunities","volume":"56","author":"Robijns","year":"2018","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.clinbiochem.2004.05.025","article-title":"Improved HPLC methodology for monitoring thiopurine metabolites in patients on thiopurine therapy","volume":"37","author":"Stefan","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1373\/clinchem.2005.050831","article-title":"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","volume":"51","author":"Dervieux","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/FTD.0b013e318283ed5d","article-title":"Improved method for therapeutic drug monitoring of 6-thioguanine nucleotides and 6-methylmercaptopurine in whole-blood by LC\/MSMS using isotope-labeled internal standards","volume":"35","author":"Kirchherr","year":"2013","journal-title":"Ther. Drug Monit."},{"key":"ref_44","unstructured":"Rosdiana, D.S., Setiabudy, R., Naibaho, S., and Louisa, M. (2018, January 19\u201322). Development and Method Validation of 6-Thioguanine and 6- Methylmercaptopurine in Erythrocytes Using LC-MS\/MS. Proceedings of the 13th International Seminar on Polymer Science and Technology (ISPST2018), Tehran, Iran."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pecher, D., Dokupilov\u00e1, S., Zelinkov\u00e1, Z., Peppelenbosch, M., Lu\u010deni\u010dov\u00e1, J., Miku\u0161ov\u00e1, V., and Miku\u0161, P. (2018). Analytical and Sample Preparation Protocol for Therapeutic Drug Monitoring of 12 Thiopurine Metabolites Related to Clinical Treatment of Inflammatory Bowel Disease. Molecules, 23.","DOI":"10.3390\/molecules23071744"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3343\/alm.2018.38.3.255","article-title":"Evaluation of Stability of Thiopurine Metabolites Using a Validated LC-MS\/MS Method","volume":"38","author":"Yoo","year":"2018","journal-title":"Ann. Lab. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0378-4347(98)00329-6","article-title":"Reversed-phase high-performance liquid chromatographic assay method for quantitating 6-mercaptopurine and its methylated and non-methylated metabolites in a single sample","volume":"716","author":"Mawatari","year":"1998","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0378-4347(92)80347-S","article-title":"High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: Quantitation of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and 6-methylmercaptopurine metabolites in a single sample","volume":"583","author":"Lennard","year":"1992","journal-title":"J. Chromatogr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/bmc.1130040202","article-title":"A reversed phase high performance liquid chromatography approach in determining total red blood cell concentrations of 6-thioguanine, 6-mercaptopurine, methylthioguanine, and methylmercaptopurine in a patient receiving thiopurine therapy","volume":"4","author":"Erdmann","year":"1990","journal-title":"Biomed. Chromatogr. BMC"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/0378-4347(93)80353-6","article-title":"High-performance liquid chromatographic determination of thiopurine metabolites of azathioprine in biological fluids","volume":"615","author":"Boulieu","year":"1993","journal-title":"J. Chromatogr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1373\/49.2.260","article-title":"Differences in Nucleotide Hydrolysis Contribute to the Differences between Erythrocyte 6-Thioguanine Nucleotide Concentrations Determined by Two Widely Used Methods","volume":"49","author":"Shipkova","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1373\/clinchem.2007.092676","article-title":"Stability of thiopurine metabolites: A potential analytical bias","volume":"54","author":"Jharap","year":"2008","journal-title":"Clin. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.jchromb.2010.03.004","article-title":"Limited stability of thiopurine metabolites in blood samples: Relevant in research and clinical practise","volume":"878","author":"Vos","year":"2010","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3109\/00365518909091557","article-title":"Analysis of 6-mercaptopurine, 6-thioguanine nucleotides, and 6-thiouric acid in biological fluids by high-performance liquid chromatography","volume":"49","author":"Bruunshuus","year":"1989","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_55","first-page":"293","article-title":"Purine nucleoside phosphorylase from human erythrocytes. 3. Inhibition by the inosine analog formycin B of the isolated enzyme and of nucleoside metabolism in intact erythrocytes and sarcoma 180 cells","volume":"4","author":"Sheen","year":"1968","journal-title":"Mol. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1046\/j.1365-2036.2000.00812.x","article-title":"Enhanced bioavailability of azathioprine compared to 6-mercaptopurine therapy in inflammatory bowel disease: Correlation with treatment efficacy","volume":"14","author":"Cuffari","year":"2000","journal-title":"Aliment. Pharmacol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:27Z","timestamp":1760143647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":56,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911885"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911885","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]}}}