Schwartz-Zimmermann Heidi E, Hametner Christian, Nagl Veronika, Slavik Veronika, Moll Wulf-Dieter, Berthiller Franz
Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna, Konrad Lorenz Str. 20, 3430, Tulln, Austria,
Anal Bioanal Chem. 2014 Dec;406(30):7911-24. doi: 10.1007/s00216-014-8252-3. Epub 2014 Oct 23.
Deoxynivalenol (DON) is a trichothecene mycotoxin regularly occurring in cereals. Rats are often used to study toxicokinetics of DON and related compounds, yet only about 30 % of the administered dose is typically recovered. Recently, it was reported that DON is partly metabolised to previously undetected DON- and deepoxy-DON (DOM) sulfonate in rats and tentative structures were proposed. The present work describes the production and characterisation of DON-, DOM- and DON-3-glucoside (D3G) sulfonates of three different series; the development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS)-based methods for determination of DON, DOM, D3G and their sulfonates in rat faeces and urine; and application of the methods to samples from a DON and D3G feeding trial with rats. In addition to previously produced DON sulfonates (DONS) 1, 2 and 3, D3G sulfonates 1, 2 and 3; and DOM sulfonates (DOMS) 2 and 3 were synthesised, purified and characterised. The developed methods showed apparent recoveries of all investigated compounds between 68 and 151 % in faeces and between 48 and 113 % in urine. The recovery of DON, D3G and their metabolites from faeces and urine of rats (n = 6) administered in a single dose of 2.0 mg/kg b.w. DON or the equimolar amount of D3G was 75 ± 9 % for the DON group and 68 ± 8 % for the D3G group. DON-, DOM- and D3G sulfonates excreted in faeces accounted for 48 and 47 % of the total amount of administered DON and D3G. Urinary excretion of sulfonates was <1 %. In both treatment groups, DONS 2 was the major metabolite 0-24 h after treatment, whereas DOMS 2 was predominant thereafter. The developed methods can also be used for investigation of DON (conjugate) sulfonate formation in other animal species.
脱氧雪腐镰刀菌烯醇（DON）是一种经常出现在谷物中的单端孢霉烯族霉菌毒素。大鼠常被用于研究DON及相关化合物的毒代动力学，但通常仅能回收约30%的给药剂量。最近有报道称，DON在大鼠体内会部分代谢为之前未检测到的DON-和脱环氧-DON（DOM）磺酸盐，并提出了初步结构。本研究描述了三个不同系列的DON-、DOM-和DON-3-葡萄糖苷（D3G）磺酸盐的制备与表征；基于液相色谱串联质谱（LC-MS/MS）的方法用于测定大鼠粪便和尿液中DON、DOM、D3G及其磺酸盐的方法开发与验证；以及将这些方法应用于大鼠DON和D3G喂养试验的样本。除了之前制备的DON磺酸盐（DONS）1、2和3外，还合成、纯化并表征了D3G磺酸盐1、2和3以及DOM磺酸盐（DOMS）2和3。所开发的方法显示，所有研究化合物在粪便中的表观回收率在68%至151%之间，在尿液中的表观回收率在48%至113%之间。以2.0 mg/kg体重的单剂量给大鼠（n = 6）施用DON或等摩尔量的D3G后，DON组大鼠粪便和尿液中DON、D3G及其代谢物的回收率为75±9%，D3G组为68±8%。粪便中排泄的DON-、DOM-和D3G磺酸盐分别占给药DON和D3G总量的48%和47%。磺酸盐的尿液排泄量<1%。在两个治疗组中，治疗后0 - 24小时内DONS 2是主要代谢物，此后DOMS 2占主导地位。所开发的方法也可用于研究其他动物物种中DON（共轭）磺酸盐的形成。
