Porous graphitic carbon based chromatography hyphenated with mass spectrometry: A new strategy for profiling thiopurine nucleotides in patients with inflammatory bowel diseases
| Autor: | Peter Mikuš, Zuzana Zelinkova, Svetlana Dokupilová, Veronika Mikušová, Daniel Pecher, Jana Lucenicova, Maikel P. Peppelenbosch |
|---|---|
| Přispěvatelé: | Gastroenterology & Hepatology |
| Rok vydání: | 2020 |
| Předmět: |
Azathioprine
02 engineering and technology 01 natural sciences Biochemistry Mass Spectrometry Analytical Chemistry medicine Environmental Chemistry Humans Nucleotide In patient Adverse effect Spectroscopy chemistry.chemical_classification Chromatography Thiopurine methyltransferase biology medicine.diagnostic_test Nucleotides 010401 analytical chemistry Inflammatory Bowel Diseases 021001 nanoscience & nanotechnology Carbon 0104 chemical sciences chemistry Therapeutic drug monitoring biology.protein Graphitic carbon Graphite 0210 nano-technology Porosity medicine.drug |
| Zdroj: | Analytica Chimica Acta, 1137, 64-73. Elsevier |
| ISSN: | 1873-4324 0003-2670 |
| Popis: | Thiopurine (TP) treatment is discontinued in up to 30% of patients suffering from inflammatory bowel diseases (IBD) due to various adverse effects. Therapeutic drug monitoring of biologically active TP metabolites, i.e. thiopurine nucleotides (TPN), can help to optimize the efficacy and safety of the TP treatment. In our work, a novel strategy for TPN profiling, based on a porous graphitic carbon (PGC) chromatography, was developed. The validated PGC-MS method was compared with ion-exchange LC-MS, a currently leading analytical approach established for the determination of TPN. The innovative approach enabled an enhancement of several key performance parameters demanded in a clinical routine use, namely (i) selectivity (time- and mass-recognition of all 12 TPN in one run), (ii) sensitivity (2-5-fold increase in intensities of the analytical signals), (iii) sample throughput (25% shorter analysis time). Application of the novel TPN profiling strategy to a pilot clinical study (12 patients) revealed significantly higher levels of 6-methylthioguanine 5′-diphosphate (MeTGDP) in non-responsive IDB patients treated with azathioprine. Some other TPN are very close to the critical level (p = 0.05) and they will need larger groups of IBD patients to confirm definitively their relevance. In conclusion, the developed PGC-MS method represents a significant improvement to currently available methods for detailed profiling of TPN and its use in bigger clinical studies should lead to a better understanding of the relationship between TPN profiles and therapeutic outcome. |
| Databáze: | OpenAIRE |
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