Core-shell LC-MS/MS method for quantification of second generation anticoagulant rodenticides diastereoisomers in rat liver in relationship with exposure of wild rats
Core-shell LC-MS/MS method for quantification of second generation anticoagulant rodenticides diastereoisomers in rat liver in relationship with exposure of wild rats
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DOI：
10.1016/j.jchromb.2016.12.028
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发表时间：
2017-01-15
影响因子：
3
通讯作者：
Lattard, Virginie
中科院分区：
文献类型：
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作者：
Fourel, Isabelle;Damin-Pernik, Marlene;Lattard, Virginie
第二代抗凝血灭鼠剂（SGAR）是世界范围内用于控制啮齿动物种群的杀虫剂，存在两种非对映异构体化学物种，因为它们拥有两个立体中心。根据生物分析指南，核壳 LC-MS/MS 多残留方法可对 5 种 SGAR 以及 3 种第一代抗凝血灭鼠剂分子的非对映异构体进行全面定量分析，已在大鼠肝脏中得到充分验证。选择核-壳柱（表面多孔颗粒）是因为它能够分离溴敌隆、苯敌螨酮、溴敌螨酮、氟香芬和敌噻酮的非对映异构体，并且对大鼠肝脏提取物具有稳健性。与全多孔色谱柱相比，非对映异构体的高选择性色谱分离有助于获得良好的信噪比，从而提高了该方法的灵敏度。分别使用 10 mM 乙酸铵和乙腈作为水/有机流动相优化了洗脱梯度。三重四极杆质量检测器已用于实现每种非对映异构体或第一代抗凝灭鼠剂的特异性和 LLOQ 为 0.92 至 2.2 ng/g。然后，我们证明了在啮齿动物消灭运动中，在法国巴黎的一个公园中捕获的野鼠（Rattusnorvegicus）不受控制的暴露所导致的大鼠肝脏中的非对映异构体比例。我们将它们与含有两种异构体的 SGAR 商业诱饵中的非对映异构体比例进行比较，结果表明两种非对映异构体之一在大鼠肝脏中几乎消失。与诱饵相比，顺式溴敌隆和反式地芬那古的比例确实降低了：分别有5/7和9/12大鼠仅具有反式溴敌隆和顺式地芬那古的肝脏残留。溴敌隆和苯芬那古两种非对映异构体的肝脏持久性因其在野生大鼠中的药代动力学差异而不同。新的核-壳LC-MS/MS方法特别适合进一步探索啮齿动物和捕食性野生动物生物样品中的非对映异构体比例，以评估实际诱饵的生态后果，探索在功效（杀死啮齿动物的能力）和非对映异构体持久性之间取得良好平衡的新配方诱饵，并有望减少非目标物种的暴露。 (C) 2016 Elsevier B.V. 保留所有权利。
Second generation anticoagulant rodenticides (SGARs), pesticides used worldwide to control rodent populations, exist in two diastereoisomer chemical species because they own two stereogenic centers. A core-shell LC-MS/MS multi-residue method for comprehensive quantitative analysis of the diastereoisomers of five SGARs as well as three first generation anticoagulant rodenticide molecules has been fully validated in liver of rats according to a bioanalytical guideline. A core-shell column (superficially porous particles) has been chosen for its ability to separate the diastereomers of bromadiolone, difenacoum, brodifacoum, flocoumafen and difethialone and for its robustness to rat liver extracts. The highly selective chromatographic separation of the diastereoisomers contributes to good signal to noise ratios and then enhances the sensitivity of the method compared to the ones of fully porous columns. An elution gradient hasbeen optimized with 10 mM ammonium acetate and acetonitrile as aqueous/organic mobile phase respectively. Triple quadrupole mass detector has been used to achieve specifity and LLOQ from 0.92 to 2.2 ng/g for each diastereoisomer, or first generation anticoagulant rodenticides. Then we evidenced diastereoisomeric ratios in liver of rats issued from not controlled exposure of wild rats (Rattus norvegicus) trapped in a French Parisian park through a campaign of rodent eradication. We compared them to diastereoisomeric ratios in SGARs commercial baits that contain both isomers, and showed that one of the two diastereoiomers had nearly disappeared in liver of rats. The proportions of cis-bromadiolone and trans-difenacoum were really lowered compared to the baits: 5/7 and 9/12 rats had only trans-bromadiolone and cis-difenacoum hepatic residues respectively. Liver persistence of the two diastereoisomers of bromadiolone and difenacoum was different due to differences in their pharmacokinetics in wild rats. The new core-shell LC-MS/MS method is particularly well adapted for further exploration of diastereoisomers ratios in rodent and predatory wildlife biological samples in order to evaluate ecological consequences of actual baits, to explore new formulated baits with a good balance between efficacity (ability to kill rodents) and diastereoisomers persistence, and hopefully to mitigate exposure of non-target species. (C) 2016 Elsevier B.V. All rights reserved.