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Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 65)

Introduction: As coumarin rodenticides, warfarin, coumatetralyl, coumafuryl, coumachlor and bromadiolone are commercially available in Japan. The coumarin rodenticides do not show direct anticoagulant action causing bleeding, but inhibit the metabolic cycle of vitamin K; the inhibition causes the interference with protein biosynthesis of vitamin K-dependent coagulant factors (II, VII, IX and X factors) in the liver, which are very important for the blood coagulation system. The lowered coagulant factors cause the bleeding deaths of the rodents [1]. Warfarin, coumatetralyl or coumafuryl is not effective with single administration, but becomes effective by repeated intakes of a small amount of each poison. | 7.8 II.7.8 Coumarin rodenticides by Shouichi Sato Introduction As coumarin rodenticides warfarin coumatetralyl coumafuryl coumachlor and bromadi-olone are commercially available in Japan. The coumarin rodenticides do not show direct anticoagulant action causing bleeding but inhibit the metabolic cycle of vitamin K the inhibition causes the interference with protein biosynthesis of vitamin K-dependent coagulant factors II VII IX and X factors in the liver which are very important for the blood coagulation system. The lowered coagulant factors cause the bleeding deaths of the rodents 1 . Warfarin coumatetralyl or coumafuryl is not effective with single administration but becomes effective by repeated intakes of a small amount of each poison for 4-5 days successively. Coumachlor and bromadiolone are much more potent and long-lasting rodenticides with long biological half-lives they provoke poisoning signs and symptoms which last for a long time only with their single administration 2 . Such a potent rodenticide is called super-warfarin . Warfarin is also very popular as an oral anticoagulant drug for treatment and prevention of thromboembolism. Although the analysis of coumarin rodenticides and anticoagulants is carried out largely by HPLC 3 4 a GC MS method for analysis of 4 rodenticides is presented in this chapter. Reagents and their preparation Coumarin rodenticides can be obtained in the forms of crystals or powder. They are slightly water-soluble and almost stable under storage at room temperature 4 . Standard compounds warfarin and coumachlor can be purchased from Sigma St. Louis MO USA coumatetralyl and bromadiolone from Wako Pure Chemical Ind. Ltd. Osaka Japan . A 100-mg aliquot each is dissolved in 100 mL methanol 1 mg mL as a stock solution. To use one of them as internal standard IS the above solution is diluted 10-fold with 50 methanol aqueous solution 100 pg mL . The above solutions should be stored at 4 C under light-shading conditions. Mixed standard .