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.