Superwarfarin (second generation) rodenticides were developed in the 1980s due to upcoming resistance of rodents to first generation products such as warfarin. Superwarfarin poisonings in humans have been described since 1984 (PubMed 159x), thereof most frequently in the US (78x) and China (20x). Brodifacoum is the most commonly applied superwarfarin rodenticide worldwide. High toxicity of superwarfarins originates from their long lasting activity as vitamin K antagonist with biological half-lives in humans of up to several weeks, e. g. brodifacoum 20 – 62 days [1].
For routine screening of urine samples we use the ToxTyperTM (Bruker Daltonics). However, rodenticides are not detected by this method. Consequently, when there is a sign of an impaired coagulation, we perform an additional screening in plasma looking for a total of 10 (super)warfarins (warfarin, phenprocoumon, coumatetralyl, coumachlor, acenocoumarol, flocoumafen, difenacoum, bromadiolon, difethiazon and brodifacoum). The measurement is performed after protein precipitation with acetonitrile/methanol and reversed phase chromatographic separation in electrospray ionization negative mode on an API4000 triple quadrupole in multiple reaction monitoring (MRM) mode (Agilent HPLC, AB Sciex) within 5 min.
In the last 10 years we performed 244 rodenticide screenings leading to 112 positive findings (73 phenprocoumon, 27 brodifacoum, 12 other). Brodifacoum positive samples may derive from intentional and unintentional ingestion in humans, animals as well as bait. Data will be shown from patients who presented in hospitals with impaired coagulation. In these cases screening of the initial urine samples using the ToxTyperTM yielded identification of patients’ known medication, but failed to detect any oral anticoagulants. Brodifacoum was then identified in plasma samples using the targeted MRM method. Concentrations exceeded 500 μg/L upon admission, and samples from time point t+26 d and t+42 d allowed for an estimation of elimination kinetics. Observations and limitations of the techniques described above will be discussed.
Literature:
[1] R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, Biomedical Publications, 11th ed., Seal Beach, 2017, 273-274