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Investigations of kinetic interactions between lipid emulsions, hydroxyethyl starch or dextran and organophosphorus compounds.

Clinical toxicology (Philadelphia, Pa.) (2013-11-10)
J Von Der Wellen, F Worek, H Thiermann, T Wille
ABSTRACT

Numerous studies demonstrated a limited efficacy of clinically used oximes in case of poisoning by various organophosphorus compounds. A broad spectrum oxime antidote covering all organophosphorus nerve agents and pesticides is still missing and effective (bio-)scavengers have not yet been marketed. The interactions of the available and clinically approved hydroxyethyl starch, dextran and lipid emulsions with organophosphorus nerve agents and pesticides were investigated in order to provide an in vitro base for the evaluation of these compounds in human organophosphorus poisoning. The degradation kinetics of organophosphorus compounds by the glucose derivatives and lipid emulsions were investigated with an acetylcholinesterase inhibition assay. The incubation of organophosphorus compounds with TRIS-Ca(2+) buffer resulted in a time-dependent degradation of the nerve agents with half-lives of 42 min for cyclosarin, 49 min for sarin, 99 min for tabun, 107 min for soman 19 h for malaoxon and 54 h for VX. In contrast, incubation with all tested compounds resulted in a stabilisation of the organophosphorus compounds. Our results suggest that binding of lipophilic organophosphorus compounds could result in a reduced spontaneous and enzyme-induced degradation of the toxic compounds. High dose lipid emulsions and glucose derivatives stabilised organophosphorus compounds in vitro.

MATERIALS
Product Number
Brand
Product Description

Malathion impurity B, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dextran from Leuconostoc mesenteroides, average mol wt 9,000-11,000
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Dextran from Leuconostoc mesenteroides, average mol wt 15,000-30,000
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Dextran from Leuconostoc mesenteroides, average mol wt 48,000-90,000
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Dextran from Leuconostoc mesenteroides, average mol wt 35,000-45,000
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Dextran from Leuconostoc mesenteroides, average mol wt 150,000
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Dextran from Leuconostoc mesenteroides, average mol wt 1,500,000-2,800,000
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Malathion, certified reference material, TraceCERT®
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Malathion solution, 100 μg/mL in cyclohexane, PESTANAL®, analytical standard
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Dextran from Leuconostoc mesenteroides, average mol wt 60,000-76,000
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Dextran from Leuconostoc spp., Mr 15,000-25,000
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Dextran, analytical standard, for GPC, 12,000
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Dextran, analytical standard, for GPC, 5,000
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Dextran, analytical standard, for GPC, 670,000
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Dextran, analytical standard, for GPC, 80,000
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Dextran, analytical standard, for GPC, 1,000
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Dextran, analytical standard, for GPC, 25,000
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Dextran, analytical standard, for GPC, 150,000
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Dextran from Leuconostoc mesenteroides, Mr ~200,000
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Dextran from Leuconostoc spp., Mr ~100,000
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Dextran, enzymatic synth.
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Dextran from Leuconostoc mesenteroides, Mr ~60,000
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Malathion, PESTANAL®, analytical standard
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Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 12,000
Supelco
Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 1,000
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Malaoxon, PESTANAL®, analytical standard
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Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 25,000
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Dextran, analytical standard, for GPC, Set Mp 1,000-400,000
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Dextran, analytical standard, for GPC, 50,000
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Dextran, analytical standard, for GPC, 410,000