PMID- 31684141 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20231019 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 21 DP - 2019 Nov 3 TI - Metabolic Profile, Bioavailability and Toxicokinetics of Zearalenone-14-Glucoside in Rats after Oral and Intravenous Administration by Liquid Chromatography High-Resolution Mass Spectrometry and Tandem Mass Spectrometry. LID - 10.3390/ijms20215473 [doi] LID - 5473 AB - Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration-time curve (AUC), 1.80 h.ng/mL; the apparent volume of distribution (V(Z)), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h.ng/mL; V(Z), 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats' plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G. FAU - Sun, Feifei AU - Sun F AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. sunff@ahau.edu.cn. AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing 100093, China. sunff@ahau.edu.cn. AD - College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China. sunff@ahau.edu.cn. FAU - Tan, Haiguang AU - Tan H AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing 100093, China. tanhaiguang1994@foxmail.com. AD - College of Life Science, Yantai University, Yantai 264005, China. tanhaiguang1994@foxmail.com. FAU - Li, Yanshen AU - Li Y AD - College of Life Science, Yantai University, Yantai 264005, China. liyanshen@tyu.edu.cn. FAU - De Boevre, Marthe AU - De Boevre M AUID- ORCID: 0000-0002-6151-5126 AD - Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Marthe.DeBoevre@UGent.be. FAU - De Saeger, Sarah AU - De Saeger S AUID- ORCID: 0000-0002-2160-7253 AD - Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Sarah.DeSaeger@UGent.be. FAU - Zhou, Jinhui AU - Zhou J AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing 100093, China. zhoujinhui@caas.cn. FAU - Li, Yi AU - Li Y AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing 100093, China. liiy01@caas.cn. FAU - Rao, Zhenghua AU - Rao Z AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. raozhenghua@caas.cn. FAU - Yang, Shupeng AU - Yang S AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing 100093, China. yangshupeng@caas.cn. FAU - Zhang, Huiyan AU - Zhang H AD - Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhanghuiyan0606@126.com. LA - eng GR - No.31702296/National Natural Science Foundation of China/ GR - No.31871718/National Natural Science Foundation of China/ PT - Journal Article DEP - 20191103 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucosides) RN - 0 (Mycotoxins) RN - 0 (zearalenone-14-glucoside) RN - 5W827M159J (Zearalenone) SB - IM MH - Administration, Intravenous MH - Administration, Oral MH - Animals MH - Biological Availability MH - Chromatography, Liquid/methods MH - Female MH - Glucosides/administration & dosage/*metabolism/pharmacokinetics MH - Male MH - Mass Spectrometry/methods MH - *Metabolome MH - Metabolomics/*methods MH - Mycotoxins/administration & dosage/*metabolism/pharmacokinetics MH - Rats, Wistar MH - Tandem Mass Spectrometry MH - Toxicokinetics MH - Zearalenone/administration & dosage/*analogs & derivatives/metabolism/pharmacokinetics PMC - PMC6862289 OTO - NOTNLM OT - bioavailability OT - masked mycotoxins OT - metabolism OT - risk assessment OT - zearalenone COIS- The authors declare no conflicts of interest. EDAT- 2019/11/07 06:00 MHDA- 2020/03/31 06:00 PMCR- 2019/11/01 CRDT- 2019/11/06 06:00 PHST- 2019/09/04 00:00 [received] PHST- 2019/10/27 00:00 [revised] PHST- 2019/10/29 00:00 [accepted] PHST- 2019/11/06 06:00 [entrez] PHST- 2019/11/07 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2019/11/01 00:00 [pmc-release] AID - ijms20215473 [pii] AID - ijms-20-05473 [pii] AID - 10.3390/ijms20215473 [doi] PST - epublish SO - Int J Mol Sci. 2019 Nov 3;20(21):5473. doi: 10.3390/ijms20215473.