Page 635 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

600 SECTION | VIII Rodenticides

VetBooks.ir including a LC-EI-MS/MS method using warfarin-D5 chlorophacinone and diphacinone. Whereas intentional
Various internal standards have been reported,
poisoning is common in dogs, secondary poisoning is com-
mon in avian and wildlife species. The mechanism of
(Yan et al., 2012) and another using Chloro-warfarin.
Contemporary mass spectroscopy methods have been action of all anticoagulant rodenticides is similar to that of
reported for use on solid samples such as hair or tissues. warfarin—i.e., inhibition of vitamin K 1 epoxide reductase,
The limits of detection (LODs) for bromadiolone and bro- resulting in the depletion of vitamin K 1 . Subsequently,
difacoum in human hair were recently reported as 0.010 this impairs the synthesis of normal clotting factors II,
and 0.025 ng/mg, respectively (Zhu et al., 2013). VII, IX, and X, and, ultimately, coagulopathy ensues due
Recent LC-ESI-MS methods have been reported for to depletion of vitamin K 1 in the liver. Diagnosis is based
the analysis of up to 10 anticoagulant rodenticides, with a on history of rodenticide exposure, clinical signs of hem-
limit of quantitation of about 5 μg/L (Grobosch et al., orrhage and coagulopathy, and chemical confirmation in
2006; Jin et al., 2007, Jin and Chen, 2006). Other LC body tissues or fluids. Treatment includes vitamin K 1 and
MS-MS methods include warfarin (Marquet et al., 2003) blood transfusion.
and flocoumafen (Boettcher et al., 2011), with an LC-
ESI-MS and HPLC-UV method to detect anticoagulant
rodenticides as low as 20 ng on column (Mesmer and REFERENCES
Flurer, 2000).
Addison, J.B., 1982. Improved method for HPLC determination of
One of the earlier MS methods used a direct probe
chlorophacinone in mouse tissue. J. Assoc. Off. Anal. Chem. 65,
technique to detect indandione residues in food animals
1299 1301.
(Braselton et al., 1992). Methods applicable to edible tis- Aisner, J., Goutsou, M., Maurer, L.H., Cooper, R., Chahinian, P., Carey, R.,
sues include an HPLC-Ion Trap/MS for indandiones et al., 1992. Intensive combination chemotherapy, concurrent chest
(Chen et al., 2010) and LC-MS/MS. Edible tissues, irradiation, and warfarin for the treatment of limited-disease small-
including bovine muscle, bovine liver, bovine fat, swine cell lung cancer: a Cancer and Leukemia Group B pilot study.
muscle, salmon, eel, freshwater clam, egg, milk, and J. Clin. Oncol. 10 (8), 1230 1236.
honey, spiked at 0.0005 0.001, with limits of quantita- Albert, C.A., Wilson, L.K., Mineau, P., Trudeau, S., Elliott, J.E., 2010.
tions of 0.0005 mg/kg for brodifacoum, 0.001 mg/kg for Anticoagulant rodenticides in three owl species from western
Canada, 1988 2003. Arch. Environ. Contam. Toxicol. 58 (2),
warfarin, coumatetralyl, and bromadiolone. Finally, an
451 459.
LC-DAD-FLD-MS method is reported to detect the
Alonso Martin, J.J., Duran Hernandez, J.M., Gimeno de Carlos, F.,
indandione chlorophacinone, and 4-hydroxy coumarins,
de la Fuente Galan, L., Munoz San Jose, J.C., Fernandez-Aviles,
bromadiolone, brodifacoum and difenacoum in liver,
F., 1997. Post-implant antithrombotic treatment after intracoronary
intestine, and muscle using FLD-DAD-ESI-MS, with lim- stents. Thrombotic occlusion. Rev. Esp. Cardiol. 50 (Suppl 2),
its of detection and quantification ranging from 9 to 31 43.
89 μg/kg (FLD-DAD) and 0.6 to 4.6 μg/kg (ESI-MS) Altay, S., Velibey, Y., Cakmak, H.A., et al., 2012. Prolonged coagulopa-
(Herna ´ndez et al., 2013b). thy related to coumarin rodenticide in a young patient: superwarfarin
poisoning. Cardiovasc. J. Afr. 23 (9), e9 e11.
AOAC, 1976a. Determination of chlorophacinone by ultraviolet spec-
troscopy, Chlorophacinone EPA-1, May 1977. Supplement to EPA
CONCLUDING REMARKS AND FUTURE
Manual of Chemical Methods for Pesticides and Devices. AOAC,
DIRECTIONS Arlington, VA.
AOAC, 1976b. Determination of diphacinone by high pressure liquid
Warfarin was the first anticoagulant rodenticide intro-
chromatography using paired-ion chromatography, Diphacinone
duced into the market soon after World War II, and was
EPA-2, May 1978. Supplement to E PA Manual of Chemical
widely used in many countries. Many other anticoagulant Methods for Pesticides and Devices. AOAC, Arlington, VA.
rodenticides with similar potency to that of warfarin were Appendino, G., Mercalli, E., Fuzzati, N., Arnoldi, L., Stavri, M.,
also synthesized (LD 50 s ranging from 10 to 50 mg/kg Gibbons, S., et al., 2004. Antimycobacterial cou-marins from the
BW). These compounds were recognized as the first- Sardinian giant fennel (Ferula communis). J. Nat. Prod. 67 (12),
generation anticoagulant rodenticides. Due to the problem 2108 2110.
of tolerance development in rodents, newer compounds Aragno, M., Tagliapietra, S., Nano, G.M., Ugazio, G., 1988.
with a greater toxicity (acute LD 50 s of 0.2 3.9 mg/kg) Experimental studies on the toxicity of Ferula communis in the rat.
Res. Commun. Chem. Pathol. Pharmacol. 59 (3), 399 402.
were developed. These compounds are called second-
Argento, A., Tiraferri, E., Marzaloni, M., 2000. Oral anticoagulants and
generation anticoagulant rodenticides, or superwarfarins.
medicinal plants: an emerging interaction [in Italian]. Ann. Ital.
Based on chemical structures, anticoagulant rodenticides
Med. Int. 15 (2), 139 143.
are classified into two categories: hydroxycoumarins and Armentano, A., Iammarino, M., Lo Magro, S., et al., 2012. Validation
indanediones. Common examples of the former group are and application of multi-residue analysis of eight anticoagulant
brodifacoum, bromadiolone, coumatetralyl, difenacoum, rodenticides by high-performance liquid chromatography with
and warfarin; examples of the latter group are fluorimetric detection. J. Vet. Diagn. Invest. 24 (2), 307 311.