Simultaneous assaying of NLG919, tryptophan and kynurenine by ultra-high performance LC–MS in pharmacokinetics and biodistribution studies

Background: Indocyanine2,3-dioxygenase (IDO) is an enzyme that can catalyze the metabolism of tryptophan (Trp) into kynurenine (Kyn), thus inhibiting the tumor immune microenvironment. Method: Based on its inhibitor, NLG919 (NLG), the authors developed a new immunomodulatory polymer micelle and established and verified an ultrahigh performance liquid chromatography–mass spectrometry method for the simultaneous determination of NLG, Trp and Kyn in mouse tumors through the ratio determination of Trp/Kyn tissue distribution and pharmacokinetics. The linear range of the method was 0.001–10 μg/ml. Results: Compared with NLG solution, the immunomodulatory polymeric drug-loaded micelles based on polystyrene-arginine showed higher Trp/Kyn ratio, more tumor aggregation and good pharmacokinetics. Conclusion: This method has been successfully applied to the simultaneous determination of Trp/Kyn and NLG in tumor tissues of mice.