RTI International, P.O. Box 12194, Research Triangle Park, NC 27709, USA.
Division of the National Toxicology Program, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
J Anal Toxicol. 2021 Jul 10;45(6):566-572. doi: 10.1093/jat/bkaa119.
Deoxynivalenol (DON) is the most widely distributed trichothecene mycotoxin in grain-based foods and animal feed. Exposure to DON is widespread as it has been detected in food sources from around the world. The objective of this work was to develop a method to quantitate DON in biological matrices and apply it in a preliminary assessment of gestational and lactational transfer of DON following exposure of pregnant rats. The method used protein precipitation followed by ultra-performance liquid chromatography-tandem mass spectrometry. The method was evaluated in male Sprague Dawley rat plasma over the concentration range ∼2-1,000 ng/mL. The method was linear (r ≥ 0.99), accurate (mean relative error ≤ ±4.9%) and precise (relative standard deviation ≤ 5.5%). The mean absolute recovery was 85.9%. The limit of detection was 0.35 ng/mL. The method was also evaluated in gestational day (GD) 18 Hsd:Sprague Dawley®SD® dam plasma and fetal homogenate (mean % relative error ≤ ±16.9; % relative standard deviation ≤ 9.5). Concentrations of DON in dam plasma stored at -80°C for at least 29 days and in fetal homogenate for at least 43 days were within 97.9 to 120% of Day 0 concentrations, demonstrating that DON is stable in these matrices. The method was used to quantitate DON in rat maternal plasma, amniotic fluid, GD 18 fetuses and postnatal day (PND) 4 pups following exposure of dams to 0 (control) and 1 mg/kg DON beginning on GD 6 and continuing through gestation and lactation for a preliminary assessment of maternal transfer. In animals exposed to 1 mg/kg/day, similar concentration of DON was found in GD 18 dam plasma and fetuses, demonstrating significant gestational transfer. The concentration of DON in PND 4 dam plasma was similar to that in GD 18 dam plasma. However, DON was not detected in PND 4 pup plasma above the limit of detection of the assay, demonstrating absence of transfer of DON to pups via lactation.
脱氧雪腐镰刀菌烯醇(DON)是谷物类食物和动物饲料中分布最广泛的一种单端孢霉烯族毒素。由于 DON 已在世界各地的食物来源中被检测到,因此其暴露是普遍存在的。本工作旨在开发一种定量检测生物基质中 DON 的方法,并应用于初步评估怀孕大鼠暴露后 DON 的妊娠和哺乳期转移。该方法采用蛋白沉淀,然后进行超高效液相色谱-串联质谱分析。该方法在雄性 Sprague Dawley 大鼠血浆中的浓度范围为 2-1000ng/ml 进行了评估。该方法呈线性(r≥0.99),准确(平均相对误差≤±4.9%),精密度良好(相对标准偏差≤5.5%)。平均绝对回收率为 85.9%。检测限为 0.35ng/ml。该方法还在妊娠 18 天 Hsd:Sprague Dawley®SD®孕鼠血浆和胎儿匀浆中进行了评估(平均相对误差≤±16.9%;相对标准偏差≤9.5%)。至少 29 天的-80°C 储存的母体血浆和至少 43 天的胎儿匀浆中的 DON 浓度与第 0 天浓度的 97.9%至 120%之间,表明 DON 在这些基质中稳定。该方法用于定量检测母体暴露于 0(对照)和 1mg/kg DON 后大鼠母体血浆、羊水、妊娠 18 天胎儿和产后第 4 天幼崽中的 DON,初步评估母体转移。在暴露于 1mg/kg/d 的动物中,在 GD 18 天母鼠血浆和胎儿中发现了类似浓度的 DON,表明存在显著的妊娠期转移。PND4 母鼠血浆中 DON 的浓度与 GD 18 天母鼠血浆中的浓度相似。然而,在 PND4 幼崽血浆中未检测到高于检测限的 DON,表明 DON 未通过哺乳期转移到幼崽中。