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 and 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.

超级华法林是第二代长效抗凝血灭鼠剂，可能会导致人类和野生动物意外中毒，部分原因是其半衰期较长。市售的超级华法林杀鼠剂是作为具有两个不对称碳的外消旋体合成的，产生四种立体异构体。为了支持对单个超级华法林立体异构体的人血浆半衰期的研究，开发了一种基于 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、苯芬那考姆和溴迪法考姆的立体异构体。使用蛋白质沉淀和离心制备人血浆样品。使用三重四极杆质谱仪上的正离子电喷雾选择反应监测，在线进行手性相 HPLC 分离，并对洗脱的立体异构体进行串联质谱定量分析。每种超级华法林的所有四种立体异构体均在 12.5 分钟内得到解析，校准曲线跨越 2-3 个数量级，定量下限在 0.87 至 2.55 ng/mL 之间。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。