Quantification of Thiopurine Metabolites in Human Erythrocytes by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
LC-MS/MS
Mercaptopurine
Therapeutic drug monitoring
Thioguanine
Journal
Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969
Informations de publication
Date de publication:
2024
2024
Historique:
medline:
4
12
2023
pubmed:
1
12
2023
entrez:
30
11
2023
Statut:
ppublish
Résumé
The thiopurine drugs, azathioprine, mercaptopurine, and thioguanine, are widely used in the treatment of several malignant and nonmalignant diseases. These inactive prodrugs undergo extensive metabolism to form active cytotoxic metabolites, which act mainly by incorporating into DNA and affecting cell replication. Thiopurine methyltransferase is a highly variable cytosolic enzyme that catalyzes the S-methylation of the thiopurine bases-an inactivating pathway. Patients with low-activity variants of TPMT can be affected by pronounced pharmacologic effects when receiving thiopurine medications. Clinical studies have reported significant interpatient variability in intracellular thiopurine metabolite concentrations in patients receiving thiopurine therapy. In this chapter, we present an LC-MS/MS method to monitor the thiopurine metabolites: 6-thioguanine nucleotides and 6-methylmercaptopurine derivatives in human erythrocytes. This method utilizes acid hydrolysis to release the bases and improves upon previously published procedures by utilizing stable isotope internal standards and a more efficient chromatographic separation.
Identifiants
pubmed: 38036845
doi: 10.1007/978-1-0716-3541-4_41
doi:
Substances chimiques
Mercaptopurine
E7WED276I5
Azathioprine
MRK240IY2L
Thioguanine
FTK8U1GZNX
Methyltransferases
EC 2.1.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
443-452Informations de copyright
© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Elion GB (1989) The purine path to chemotherapy. Science 244(4900):41–47
doi: 10.1126/science.2649979
pubmed: 2649979
Lennard L (1992) The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 43(4):329–339
doi: 10.1007/BF02220605
pubmed: 1451710
Zaza G, Cheok M, Krynetskaia N, Thorn C, Stocco G, Hebert JM, McLeod H, Weinshilboum RM, Relling MV, Evans WE, Klein TE, Altman RB (2010) Thiopurine pathway. Pharmacogenet Genomics 20(9):573–574
doi: 10.1097/FPC.0b013e328334338f
pubmed: 19952870
pmcid: 3098750
Evans WE (2004) Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Ther Drug Monit 26(2):186–191
doi: 10.1097/00007691-200404000-00018
pubmed: 15228163
Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui CH, Stein CM, Moyer AM, Evans WE, Klein TE, Antillon-Klussmann FG, Caudle KE, Kato M, Yeoh AEJ, Schmiegelow K, Yang JJ (2019) Clinical Pharmacogenetics Implementation Consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther 105(5):1095–1105
doi: 10.1002/cpt.1304
pubmed: 30447069
Liu C, Yang W, Pei D, Cheng C, Smith C, Landier W, Hageman L, Chen Y, Yang JJ, Crews KR, Kornegay N, Karol SE, Wong FL, Jeha S, Sandlund JT, Ribeiro RC, Rubnitz JE, Metzger ML, Pui CH, Evans WE, Bhatia S, Relling MV (2017) Genomewide approach validates thiopurine methyltransferase activity is a monogenic pharmacogenomic trait. Clin Pharmacol Ther 101(3):373–381
doi: 10.1002/cpt.463
pubmed: 27564568
Dong XW, Zheng Q, Zhu MM, Tong JL, Ran ZH (2010) Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease. World J Gastroenterol 16(25):3187–3195
doi: 10.3748/wjg.v16.i25.3187
pubmed: 20593505
pmcid: 2896757
Sandborn WJ (2001) Rational dosing of azathioprine and 6-mercaptopurine. Gut 48(5):591–592
doi: 10.1136/gut.48.5.591
pubmed: 11302950
pmcid: 1728293
Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SE, Lilleyman J, Richards SM, Medical Research Council; National Cancer Research Network Childhood Leukaemia Working Party (2006) Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet 368(9544):1339–1348
doi: 10.1016/S0140-6736(06)69558-5
pubmed: 17046466
Ebbesen MS, Nygaard U, Rosthøj S, Sørensen D, Nersting J, Vettenranta K, Wesenberg F, Kristinsson J, Harila-Saari A, Schmiegelow K (2017) Hepatotoxicity during maintenance therapy and prognosis in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 39(3):161–166
doi: 10.1097/MPH.0000000000000733
pubmed: 28060115
Dervieux T, Meyer G, Barham R, Matsutani M, Barry M, Boulieu R, Neri B, Seidman E (2005) 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 51(11):2074–2084
doi: 10.1373/clinchem.2005.050831
pubmed: 16166171
Dervieux T, Boulieu R (1998) 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 44(12):2511–2515
doi: 10.1093/clinchem/44.12.2511
pubmed: 9836719