Mass spectrometry characterization of anticoagulant rodenticides and hydroxyl metabolites

Abstract

Rationale Anticoagulant rodenticides (ARs) are used worldwide for rodent population control to protect human health and biodiversity, and to prevent agricultural and economic losses. Rodents may develop a metabolic resistance to ARs. In order to help understand such metabolic resistance, mass spectrometry was used to position the hydroxylated group of hydroxyl metabolites of second‐generation ARs (SGARs). Methods Most AR pesticides are derived from the 4‐hydroxycoumarin/thiocoumarin family. We used low‐resolution and high‐resolution mass spectrometry to understand the fragmentation pathways of the ARs and their respective metabolites, and to better define the structure of their tandem mass spectrometry product ions. Results Seven specific product ions were evidenced for five ARs, with their respective chemical structures. Those ions were obtained as well from the mass spectra of the hydroxyl metabolites of four SGARs, difenacoum (DFM), brodifacoum (BFM), difethialone (DFTL) and flocoumafen (FLO), with different positions of the hydroxyl group. Conclusions The differences in chemical structure between DFM on the one hand and BFM, FLO and DFTL on the other could explain the differences in bioavailability between these two groups of molecules. The defined product ions will be used to investigate the part played by the metabolic issue in the field resistance of SGARs.

Thiocoumarins: From the Synthesis to the Biological Applications

“…In the 1980s, thiocoumarins already had clinical use as haemorrhagic agents, anticoagulants (interfering with vitamin K-dependent coagulation factors), and antiallergic agents [ 5 ]. In fact, some thiocoumarin derivatives found important applications as anticoagulant rodenticides pesticides [ 6 ].…”

“…7-Hydroxy-4-methylthiocoumarin is the precursor for a pyrano [ 6 , 7 ] thiocoumarins, reported for their anti-HIV potential [ 36 ]. From this series, an excellent derivative, with an EC 50 in the low nanomolar range, was described.…”

Biomarkers Potency to Monitor Non-target Fauna Poisoning by Anticoagulant Rodenticides

“…Non-invasive detection and quantification of AR can be performed in plasma (85,(152)(153)(154)(155), milk (85,124), and feces (37,154,156,157), while invasive analysis can also detect AR in target organs, especially in the liver, that is widely used for forensics investigation especially for wildlife (61, 130, 131, 158-160), but also in muscle, fat, or bone (155). Analyses are usually performed by high performance liquid chromatography that can be coupled with UV, fluorescence (152) or mass spectrometry (157,(160)(161)(162) detection. AR screenings can be relevant to confirm and quantify exposure to these chemicals.…”

“…The measurement of vitamin K forms is usually performed by chromatography (liquid, high performance), that can be coupled with fluorescence (152) or mass spectrometry (157,(160)(161)(162) detection. The determination of vitamin K concentrations can be done in plasma, as the different forms circulate in the plasma in live animals.…”