Background Thiopurine metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine (6MMP), are monitored to aid therapeutic management of thiopurine drugs. At Manchester University NHS Foundation Trust (MFT), thiopurine metabolites are measured by high performance liquid chromatography with ultraviolet detection (HPLC-UV). Whole blood samples are lysed and subjected to hydrolysis with derivatisation of 6MMP before HPLC-UV detection at 304nm for the 6MMP-derivative and 342nm for 6TG. For some samples, 6MMP cannot be reported due to a chromatographic interference at 304nm co-eluting with the 6MMP peak. An investigation was performed to identify the interfering compound. Methods Patient medication histories were examined to identify candidate compounds for the interference. Candidate compounds were spiked into blood at supraphysiological concentrations and tested on the assay. Results Metronidazole was identified as being prescribed to all patients whose samples demonstrated the interference. Metronidazole and its metabolite, hydroxymetronidazole, were spiked into blood. HPLC-UV analysis of spiked blood demonstrated similar UV absorbance patterns to those seen in patient samples with the interference. Hydroxymetronidazole co-eluted with 6MMP causing interference in the measurement. Conclusion Metronidazole and its major metabolite can interfere with 6MMP measurement by HPLC-UV analysis at 304 nm.
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Background Thiopurine metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine (6MMP), are monitored to aid therapeutic management of thiopurine drugs. At Manchester University NHS Foundation Trust (MFT), thiopurine metabolites are measured by high performance liquid chromatography with ultraviolet detection (HPLC-UV). Whole blood samples are lysed and subjected to hydrolysis with derivatisation of 6MMP before HPLC-UV detection at 304nm for the 6MMP-derivative and 342nm for 6TG.
View Article and Find Full Text PDFResponse to azathioprine treatment in autoimmune hepatitis is dependent on glutathione transferase genotypes.
Dig Liver Dis
January 2025
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Laboratory Medicine, Region Jönköping County, Jönköping, Sweden. Electronic address:
Background: Azathioprine (AZA) is part of the standard treatment for autoimmune hepatitis (AIH). The first step in the complex bioconversion of AZA to active metabolites is mediated by glutathione transferases (GSTs).
Aims: Elucidate the association between GSTM1 and GSTT1 copy number variation (CNV), genetic variation in GSTA2, GSTP1, and inosine-triphosphate-pyrophosphatase, and the response to AZA in AIH.
A Rapid and Reliable Absorbance Assay to Identify Drug-Drug Interactions with Thiopurine Drugs.
Metabolites
December 2024
Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Background: Thiopurine methyltransferase (TPMT) plays a crucial role in the detoxification of thiopurine drugs, including the antimetabolites azathioprine and 6-mercaptopurine (6-MP) used to treat autoimmune diseases and various cancers. These drugs interfere with DNA synthesis by inhibiting the production of purine-containing nucleotides, leading to the death of rapidly dividing cells. TPMT inactivates thiopurine drugs by methylating at the thiol group.
View Article and Find Full Text PDFDramatic Changes in Thiopurine Metabolite Levels in a Patient With Inflammatory Bowel Disease Treated With Tirzepatide for Weight Loss.
ACG Case Rep J
November 2024
Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL.
Thiopurines can be used to maintain remission in patients with inflammatory bowel disease. Thiopurines require regular blood count monitoring and, in specific patients, thiopurine metabolites for assessment of optimization and safety. We present the case of a 42-year-old woman with ulcerative colitis postcolectomy and ileal pouch-anal anastomosis with subsequent antibiotic-resistant diffuse pouchitis and prepouch ileitis.
View Article and Find Full Text PDFContemporary and prospective use of azathioprine (AZA) in viral, rheumatic, and dermatological disorders: a review of pharmacogenomic and nanotechnology applications.
Naunyn Schmiedebergs Arch Pharmacol
November 2024
Department of Pharmacy Practice, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research Pimpri, Pune, Maharashtra, India.
Article Synopsis
- Azathioprine (AZA), commonly used for autoimmune disorders and organ transplants, shows potential for modern applications in viral, rheumatic, and skin diseases.
- Advances in pharmacogenomics and nanotechnology may enhance AZA's effectiveness while reducing side effects, particularly by utilizing the active metabolites 6-mercaptopurine and 6-thioguanine.
- The study suggests that personalized medicine approaches, including genetic testing and innovative drug delivery systems, can improve treatment outcomes for conditions like systemic lupus erythematosus and psoriasis.
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