The metabolism of olaquindox in rats, chickens and pigs.
Olaquindox is a growth-promoting feed additive for food-producing animals. Its toxicities were reported to be closely related to the metabolism. To provide the interpretation of toxicities in animals, this study explored the metabolism of olaquindox in rats, chickens and pigs of different genders by qualitative metabolite profiling. Animals were fed olaquindox in an oral dose, and then their urine, plasma, feces, liver, kidney and muscle were collected. Liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry was used for structural investigation and identification of metabolites. The structures of metabolites were elucidated based on the accurate MS² spectra and comparison of their changes in accurate molecular masses and fragment ions with those of parent drug or metabolite. A total of 18, 18 and 16 metabolites of rats, chickens and pigs were identified, respectively. Among the identified metabolites, 8 known metabolites were confirmed as an early study had stated, and 15 metabolites were found for the first time in vivo. The major metabolic pathways of olaquindox were proposed to be N-O reduction and oxidation of hydroxyl to carboxylic acid followed by N-O reduction. The qualitative species difference on the metabolite profiles of olaquindox among the three species was observed. However, metabolite profiles of olaquindox appeared to be qualitatively similar between female and male for the same species. The proposed metabolic pathways of olaquindox in animals will provide comprehensive data to clarify the metabolism of olaquindox among different species, and will give scientific explanation for toxicities and residues of olaquindox.
National Reference Laboratory of Veterinary Drug Residues (HZAU)/MAO Key Laboratory of Food Safety Evaluation, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Zhao-Ying
ZY
Liu
Ling-Li
LL
Huang
Xiao-Ni
XN
Zhou
Dong-Mei
DM
Chen
Yan-Fei
YF
Tao
Hua-Hai
HH
Zhang
Zong-Hui
ZH
Yuan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D002645:Chickens; D005243:Feces / Q000737:chemistry; D005260:Female; D006133:Growth Substances / Q000493:pharmacokinetics; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D011810:Quinoxalines / Q000032:analysis / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D013552:Swine
D000900:Anti-Bacterial Agents; D006133:Growth Substances; D011810:Quinoxalines; C013168:olaquindox