Determination of thiopurine S-methyltransferase (TPMT) activity by comparing various normalization factors: reference values for Estonian population using HPLC-UV assay

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Kersti OselinUno Mäeorg

Abstract

Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) is the key enzyme in the metabolism of thiopurine drugs. Determination of TPMT activity has been used for the individualization of thiopurine dose. We developed HPLC-UV assay for the determination of TPMT activity in human erythrocytes using 6-mercaptopurine as a substrate. Various extraction and chromatographic conditions were compared. In-house developed extraction with acetonitrile provided the lowest limit of quantification. TPMT activity was determined in 99 previously genotyped healthy Estonians. TPMT activity was expressed as the formation of 6-methylmercaptopurine ng/ml/h and normalized either to haemoglobin, haematocrit, erythrocyte count or protein content. The receiver-operating characteristic curve analysis revealed similar accuracy values for TPMT activity in predicting heterozygous and wild type individuals for each method of calculation. In healthy Estonians, TPMT activity varied from 21.5 to 129.6 ng/ml/h. For heterozygous individuals (n = 18), TPMT activity was 48.1 +/- 11.7 ng/ml/h. Wild type individuals (n = 81) revealed significantly higher TPMT activity 79.3 +/- 20.7 ng/ml/h (P < 0.001). This sensitive HPLC assay for quantitative determination of TPMT activ...Continue Reading

References

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Citations

Sep 15, 2009·Clinical Biochemistry·Natasa Karas-KuzelickiIrena Mlinaric-Rascan
Oct 31, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jianqiang XuJan-Christer Janson
Aug 22, 2013·British Journal of Clinical Pharmacology·Lynne Lennard
Jul 9, 2008·Clinical Chemistry and Laboratory Medicine : CCLM·Riin TammAndres Metspalu
Feb 16, 2018·BMC Research Notes·Ayorinde Adehin, Oluseye O Bolaji
Jun 8, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kersti Oselin, Kaili Anier
Mar 23, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·S M IllamolaN Pallet

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