Methods for Determination of Reactive Metabolites of Thiopurines

Abstract

Background: This Review Represents A Critical And Constructive Analysis Of Literature In The Content
Of Methods For Determination Of Reactive Metabolites Of Thiopurines. The Review Is Generated Through
Summary, Classification, Analysis And Comparison Of Already Existing Material And Researches On Field.
Methods: Databases As Scopus, Pubmed, Medline And Web Of Science Were Used To Extract Data For The
Review. Search Terms Like “Methods For Determination Of Metabolites”, “Thiopurines” And “Reactive
Metabolites” Were Used. Out Of 160 Research Articles Screened, 20 Most Relevant Studies Are Included
In This Review.
Conclusion: Determining Thiopurine Metabolites Level Is Crucial On Improving Patients’ Safety, Quality
And Efficacy Of Treatment, Measure Patients’ Adherence To Therapy, Optimize Thiopurine Dosage By
Either Finding Safer/Higher Doses If Remission Is Not Achieved, Or By Determining Dose Reductions
When Adverse Treatment Outcomes Occur.
Thiopurine Metabolites Are Measured By High-Performance Liquid Chromatography (Hplc), Through
Determining Metabolites’ Concentration In Hemolysate. Thioguanine Nucleotides (Tgn) And The
Methylated Thioinosine Derivatives Are Not Measured Directly, Rather The 6-Thioguanine (Tg) For Tgn,
And 4-Amino-5-(Methylthio) Carbonyl Imidazole (Amtci) For Methylated Thioinosine Derivatives Are
Measured.
There Is A Misconception Among Patients And Healthcare Providers, That Determining Thiopurine
Metabolites Level Provides Assurance On Optimal Dosing Which Can Be Used To Prevent Adverse
Thiopurine Treatment Outcomes. Despite This Assumption, Clearly Most Of The Thiopurine Adverse
Effects Are Not Directly Related To Their Metabolites As 6-Tgn Or 6-Mmp Levels. Clinical Experience Has
Demonstrated That Infections Associated With Thiopurines Do Not Regularly Correlate With Leukopenia,
And Elevated Transaminases Can Occur Despite Normal 6-Mmp Levels.