TPMT

Background Information

 

There is growing interest in the measurement of thiopurine S-methyltransferase (TPMT)  activity in erythrocytes to ensure appropriate treatment with  thiopurine drugs such as azathioprine.

The cytosolic enzyme TPMT metabolises thiopurines to inactive metabolites. The dose of azathioprine given needs to be high enough to maintain therapeutic levels despite these losses, but some people do not have this enzyme or have it at reduced activity.

TPMT exhibits genetic variation giving rise to a trimodal distribution, with 0.3% of the population lacking the enzyme and a further 11% having low activity. Screening to detect these patients prior to treatment means serious side effects may be averted. The measurement of TPMT is generally undertaken at a referral laboratory.

The assay at City Hospital is designed for analysing large numbers of patient samples. From October 2003 it carries the CE mark, the assay having been registered with the MHRA.

A useful discussion string following a paper in the BMJ can be read at:

http://bmj.bmjjournals.com/cgi/eletters/330/7487/350

International QA Scheme

We are involved with UK NEQAS who are setting up an international quality assessment scheme for TPMT activity. If you would like to participate then please contact: 

Jane French,Principal EQA Scientist, UK NEQAS for TPMT Phenotyping
Email: tpmt@ukneqas.org.uk

 

Metabolites of Thiopurine Drugs

·         We now offer a service for 6-thioguanine nucleotides (6-TGN) which can be  used to assess the levels of active drug metabolites being achieved.  

 

Research Posters, Papers & Presentations

 

Details of our service were recently given at the ACB Wales meeting in Llandudno.

Ford LT, Berg JD. Determination of thiopurine S-methyltransferase activity in erythrocytes using 6-thioguanine as substrate and a non extraction liquid chromatographic technique. J Chromatog 2003; 798: 111-15

Ford, LT & Berg JD (2004). Establishing a referral service for thiopurine thiopurine S-methyltransferase phenotyping. Proc ACB Nat. Meeting. Abstract 13, 46.

Ford, LT Samra, M Berg JD (2004).  Comparison of thiopurine thiopurine S-methyltransferase activity using different methods for preparing red blood cell lysates.

Jeffray, CM.,Ford, LT. & Berg JD.  (2004). Erythrocyte thiopurine thiopurine S-methyltransferase stability under different environmental conditions: recommendations for appropriate transport and storage. Proc ACB Nat. Meeting. Abstract 15, 47.

Prout, CH., Ford, LT, Gaffney, D. & Berg JD. (2004). Whose TPMT activity is it anyway? Proc ACB Nat. Meeting. Abstract 40, 94.

Berg, JD. & Ford LT. (2004).The first CE marked NHS in-house assay: the central role of the technical file. Proc ACB Nat. Meeting. Abstract 85, 113.

Ford, LT., Cooper, SC., Lewis, MJV. & Berg JD. (2004). Reference intervals for thiopurine S-methyltransferase activity in red blood cells using 6-thioguanine as substrate and a rapid non-extraction liquid chromatographic technique. 2004; 41; 303-8.

Ford L, Prout C, Gaffney D, & Berg J. Whose TPMT activity is it anyway? Annal Clin Biochem. Clinical Case 2004, 41: 498-500.

Ford L, Graham V, Berg JD. Comparison of HPLC fluorescence, UV and mass spectrometry detection methods for the determination of TPMT activity. Clin Chim Acta 2005; 355: S241

Mohammad P, Ford L, Berg JD. Development of an isocratic HPLC method with UV detection for the measurement of erythrocyte 6-thioguanine and 6-mercaptopurine. Clin Chim Acta 2005; 355: S385

Graham V, Ford L, Berg JD. Twelve months of a TPMT Referral Service; Has it made a difference? Clin Chim Acta 2005;  355: S387

Ford L, Graham V, Berg JD. Screening patient TPMT activity using a single drop of blood. Clin Chim Acta 2005;  355: S387

Jeffray CM, Ford LT, Berg JD. Understanding preanalytical factors affecting the variability in TPMT activity. Clin Chim Acta 2005; 355: S388

Berg JD, Burrows J, Ford L.  Changes in temperature experienced by clinical samples during international postal transit using the Signatrol temperature data logger. Clin Chem Acta 2005; 355: S401

 

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