Determination of kynurnine and tryptophan, biomarkers of indoleamine 2,3-dioxygenase by LC–MS/MS in plasma and tumor
| Autor: | Xuhui Zhuang, Guangying Du, Wenrong Liu, Liang Ye, Heyuan Sun, Lina Dong, Wenyan Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Clinical Biochemistry Pharmacology 01 natural sciences Analytical Chemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tandem Mass Spectrometry Neoplasms Lc ms ms Animals Indoleamine-Pyrrole 2 3 -Dioxygenase General Pharmacology Toxicology and Pharmaceutics Indoleamine 2 3-dioxygenase Kynurenine Mice Inbred BALB C Tumor Immune Escape 010401 analytical chemistry Tryptophan General Medicine 0104 chemical sciences Medical Laboratory Technology chemistry 030220 oncology & carcinogenesis Biomarkers Blood Chemical Analysis Chromatography Liquid |
| Zdroj: | Bioanalysis. 10:1335-1344 |
| ISSN: | 1757-6199 1757-6180 |
| DOI: | 10.4155/bio-2018-0041 |
| Popis: | Aim: Tryptophan (Trp) and kynurnine (Kyn) are a pair of biomarkers for indoleamine 2,3-dioxygenase which closely related to the tumor immune escape. To evaluate the effect of drugs on the indoleamine 2,3-dioxygenase activity, the specific and accurate LC–MS/MS methods were developed and validated for simultaneous determination Kyn and Trp in mouse plasma and tumor tissues using surrogate analytes Kyn-d4 and Trp-d5 calibrators. Results: Plasma and tumor homogenates samples were pretreated with the solid phase extraction which assured the method having high recovery (>90% in plasma and >80% in tumor) and no matrix effect. The methods were validated for specificity, linearity, accuracy and precision, recovery, matrix effect and stability using surrogate analytes Kyn-d4 and Trp-d5 in authentic matrices. Conclusion: The validated methods have been successfully applied to the pharmacodynamic study of INCB024360 in CT26 tumor bearing mice after single dose and multiple dosing. |
| Databáze: | OpenAIRE |
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