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建立 UPLC-MS-MS 分析方法定量检测脱氧雪腐镰刀菌烯醇:大鼠妊娠期和哺乳期转移的初步评估。

Development of an Analytical Method for Quantitation of Deoxynivalenol by UPLC-MS-MS: A Preliminary Assessment of Gestational and Lactational Transfer in Rats.

机构信息

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.

出版信息

J Anal Toxicol. 2021 Jul 10;45(6):566-572. doi: 10.1093/jat/bkaa119.

Abstract

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.

摘要

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。

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本文引用的文献

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Deoxynivalenol transport across the human placental barrier.脱氧雪腐镰刀菌烯醇穿过人类胎盘屏障的转运。
Food Chem Toxicol. 2011 Sep;49(9):2046-52. doi: 10.1016/j.fct.2011.05.016. Epub 2011 May 19.
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Deoxynivalenol and its toxicity.脱氧雪腐镰刀菌烯醇及其毒性。
Interdiscip Toxicol. 2010 Sep;3(3):94-9. doi: 10.2478/v10102-010-0019-x.

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