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Combinatorial approach of LC-MS/MS and LC-TOF-MS for uncovering in vivo kinetics and biotransformation of ochratoxin A in rat

文献类型： 外文期刊

作者： Han, Zheng 1 ; Zhao, Zhiyong 1 ; Shi, Jianxin 2 ; Liao, Yucai 3 ; Zhao, Zhihui 1 ; Zhang, Dabing 2 ; Wu, Yongning 4 ; De 1 ;

作者机构： 1.Shanghai Acad Agr Sci, Inst Agrifood Stand & Testing Technol, Shanghai 201403, Peoples R China

2.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Bor Luh Food Safety Ctr, Shanghai 200240, Peoples R China

3.Huazhong Agr Univ, Coll Plant Sci & Technol, Wuhan 430070, Hubei, Peoples R China

4.Chinese Ctr Dis Control & Prevent, Natl Inst Nutr & Food Safety, Beijing 100050, Peoples R China

5.Univ Ghent, Lab Food Anal, Fac Pharmaceut Sci, B-9000 Ghent, Belgium

关键词： Biotransformation;Kinetics;Liquid chromatography coupled with time of flight mass spectrometry;Liquid chromatography-tandem mass spectrometry;Ochratoxin A

期刊名称：JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES （ 影响因子：3.205； 五年影响因子：3.068 ）

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收录情况： SCI

摘要： A combinatorial platform of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography coupled with time of flight mass spectrometry (LC-TOF-MS) has been developed to investigate the in vivo kinetics and biotransformation of ochratoxin A (OTA) in rats. The stable isotope dilution LC-MS/MS method was first validated by determining the linearity (R~2≥0.9990), sensitivity (lower limit of quantitation of 0.05ngmL~(-1)), accuracy (83.3-108.3), precision (RSD≤15.6%) and stability (≥75.0%), and was approved for the determination OTA in plasma, heart, liver, spleen, lung, kidney and brain with a run time of 7.0min. Simultaneously, an LC-TOF-MS method could unambiguously identify the metabolites of OTA in a total run time of 14min. The subsequent studies on kinetics and distribution after oral administration of 0.2mg/kg b.w. OTA in rat indicated that OTA could reach a maximum value of 1932.4±124.9ngmL-1 within 5h due to its fast absorption, and then was slowly eliminated in plasma with a half-life time (t_(1/2)) of 75.6±29.0h. Results of tissue accumulation after a daily oral administration of 0.1mg/kg b.w. OTA during 20 days showed that the highest concentration of OTA was observed in lung (95.9±13.7ngg~(-1)), followed by liver (76.0±9.7ngg~(-1)), heart (62.0±4.2ngg~(-1)) and kidney (55.7±4.7ngg~(-1)). Furthermore, three less toxic metabolites of OTA were clearly identified: Ochratoxin β (OTβ) and ochratoxin B (OTB) methyl ester were found in kidney and spleen, respectively, while phenylalanine was detected in heart and kidney. Thus, a possible metabolic pathway of OTA was proposed. The above achieved results justified that the application of combinatorial LC-MS/MS and LC-TOF-MS methods are valuable tools to uncover the kinetics and metabolism of OTA for the interpretation of toxicological findings in animals and extrapolation of the resulting data as reference to humans.

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