Determination of kynurnine and tryptophan, biomarkers of indoleamine 2,3-dioxygenase by LC-MS/MS in plasma and tumor.

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.

• Authors: Wenyan Wang, Xuhui Zhuang, Wenrong Liu, Lina Dong, Heyuan Sun, Guangying Du, Liang Ye
• Journal: Bioanalysis (Bioanalysis) Vol. 10 Issue 16 Pg. 1335-1344 (Aug 01 2018) ISSN: 1757-6199 [Electronic] England
• PMID: 30130131 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Kynurenine
• Tryptophan

Topics

• Animals
• Biomarkers (blood, metabolism)
• Blood Chemical Analysis (methods)
• Chromatography, Liquid
• Indoleamine-Pyrrole 2,3,-Dioxygenase (antagonists & inhibitors, metabolism)
• Kynurenine (blood, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasms (blood)
• Tandem Mass Spectrometry
• Tryptophan (blood, metabolism)