Chiral liquid chromatography-tandem mass spectrometry analysis of superwarfarin rodenticide stereoisomers - Bromadiolone, difenacoum and brodifacoum - In human plasma.
Chiral liquid chromatography-tandem mass spectrometry analysis of superwarfarin rodenticide stereoisomers - Bromadiolone, difenacoum and brodifacoum - In human plasma.
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DOI：
10.1016/j.jchromb.2021.122529
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发表时间：
2021-02-15
期刊：
影响因子：
--
通讯作者：
van Breemen RB
中科院分区：
文献类型：
--
作者：
Nosal DG;Feinstein DL;van Breemen RB
Superwarfarins是第二代长效抗凝血灭鼠剂，部分由于其半衰期延长，可能导致意外的人类和野生动物毒性。市售的超级杀鼠灵灭鼠剂被合成为具有两个不对称碳的外消旋体，产生四种立体异构体。为了支持个体超级华法林立体异构体的人血浆半衰期的研究，开发了基于LC-MS/MS的方法来分离和定量商业上重要的超级华法林溴敌隆、敌鼠灵和溴鼠灵的立体异构体。使用蛋白沉淀和离心制备人血浆样品。手性相HPLC分离进行在线串联质谱定量分析的洗脱立体异构体使用选择性反应监测与正离子电喷雾在三重四极杆质谱仪。每种超级华法林的所有四种立体异构体在12.5分钟内分离，校准曲线跨越2 - 3个数量级，定量下限为0.87 - 2.55 ng/mL。该方法用于测定吸入受超级华法林污染的合成大麻素产品的患者血浆中超级华法林立体异构体的半衰期。这些数据可用于指导更安全的下一代抗凝血灭鼠剂立体异构体的开发。
Superwarfarins are second-generation long-acting anticoagulant rodenticides that can cause unintended human and wildlife toxicity due, in part, to their prolonged half-lives. Commercially available superwarfarin rodenticides are synthesized as racemates with two asymmetric carbons, producing four stereoisomers. To support studies of human plasma half-lives of individual superwarfarin stereoisomers, a method was developed based on LC-MS/MS to separate and quantify stereoisomers of the commercially important superwarfarins bromadiolone, difenacoum and brodifacoum. Human plasma samples were prepared using protein precipitation and centrifugation. Chiral-phase HPLC separation was carried out on-line with tandem mass spectrometric quantitative analysis of the eluting stereoisomers using selected-reaction monitoring with positive ion electrospray on a triple quadrupole mass spectrometer. All four stereoisomers of each superwarfarin were resolved within 12.5 min with calibration curves spanning 2 – 3 orders of magnitude and lower limits of quantitation between 0.87 – 2.55 ng/mL. This method was used to determine the half-lives of superwarfarin stereoisomers in plasma from patients who had inhaled synthetic cannabinoid products contaminated with superwarfarins. These data may be used to guide the development of safer next generation anticoagulant rodenticides stereoisomers.
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影响因子：
64.8
作者：
HADLER, MR;SHADBOLT, RS
通讯作者：
SHADBOLT, RS
影响因子：
3.3
作者：
Gummin, David D.;Mowry, James B.;Ryan, Mark L.
通讯作者：
Ryan, Mark L.
影响因子：
2.9
作者：
FASCO, MJ;PRINCIPE, LM;FRIEDMAN, PA
通讯作者：
FRIEDMAN, PA
影响因子：
158.5
作者：
Kelkar, Amar H.;Smith, Nichole A.;Roberts, Jonathan C.
通讯作者：
Roberts, Jonathan C.
DOI：
10.1016/j.jchromb.2016.12.028
发表时间：
2017-01-15
影响因子：
3
作者：
Fourel, Isabelle;Damin-Pernik, Marlene;Lattard, Virginie
通讯作者：
Lattard, Virginie