**4. Materials and Methods**

#### *4.1. Chemicals and Reagents*

All used solvents and reagents were LC–MS grade. Water (H2O), acetonitrile (ACN), formic acid (FA), and ammonium formate (CAS 540-69-2) were obtained from Sigma Aldrich (St. Louis, MO, USA). The stable isotope-labeled (SIL) internal standard 13C15N2- 8-hydroxy-2 -deoxyguanosine (13C15N2-8-OH-dG) was obtained from Toronto Research Chemicals (Toronto, ON, Canada). 15N4-hypoxanthine (15N4-Hyp), L-tyrosine-(phenyl-d4) (d4-L-Tyr), and 15N4-inosine (15N4-I) were purchased from Cambridge Isotope Laboratories, Inc., (Tewksbury, MA, USA). L-kynurenine sulfate: H2O (ring-d4, 3,3-d2) (d6-KYN) and D2O were acquired from Cambridge Isotope Laboratories, Inc. (Andover, MA, USA). Anthranilic acid-ring-13C6 ( 13C6-AA) and 3-(trimethylsilyl)-2,2,3,3-d propionic acid (TSP) were purchased from Sigma Aldrich (Schnelldorf, Germany). 15N,13C2-3-Hydroxy-DLkynurenine (15N-13C2-OH-KYN) was obtained from AMRI (Albany, NY, USA).
