Wenyan Wang1, Xuhui Zhuang1, Wenrong Liu1, Lina Dong1, Heyuan Sun1, Guangying Du1, Liang Ye2. 1. School of Pharmacy, Key Laboratory of Molecular Pharmacology & Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System & Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, Shandong, PR China. 2. Institute of Toxcicology, Binzhou Medical University, Yantai 264003, Shandong, PR China.
Abstract
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.
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.
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