In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

Ochratoxin A (OTA) is a mycotoxin that frequently contaminates a wide variety of food and feedstuffs. The metabolism of OTA greatly affects fate and toxicity in humans and animals, because of its possible carcinogenic character (International Agency for Research on Cancer (IARC), group 2B). To completely characterize the metabolites of OTA, the metabolism of OTA in liver microsomes of rats, chickens, swine, goats, cows, and humans was investigated using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UPLC-Q/TOF-MS). In addition, an in vivo comparative metabolism study of OTA was performed among rats and chickens after oral administration of OTA. As a result, a clear metabolic profile of OTA in different species was proposed, and a total of eight metabolites were identified, of which three hydroxylated metabolites at the phenylalanine moiety were discovered for the first time (preliminarily identified as 9'-OH-OTA, 7'-OH-OTA, and 5'-OH-OTA). Considerable amounts of 7'-OH-OTA were detected in different species' liver microsomes, especially in chickens and humans. Moreover, the metabolism of OTA in chickens was elucidated for the first time in the present study. The 7'-OH-OTA proved to be the main metabolite in vitro and in vivo in chickens. Furthermore, the 4(S)-OH-OTA isomer was the major one, and 4(R)-OH-OTA the minor metabolite in chickens, which was different from others where 4R was the major. OTA undergoes metabolism via three different pathways, namely hydroxylation, dechlorination, and conjugation. The proposed metabolic pathways of OTA in various species provide the scientific community useful data for the toxicological safety evaluation of OTA among different species, and will further facilitate the food safety evaluation of OTA.