Thiabendazole, formation

Detection in liquid chromatography is mostly performed by fluorescence and/or ultraviolet absorption. In a few instances, electrochemical detection has also been employed (357, 368). For compounds that exhibit inherent intense fluorescence such as albendazole and metabolites (319, 320, 338, 355), closantel (344), and thiabendazole and metabolites (378), fluorometric detection is the preferred detection mode since it allows higher sensitivity. Compounds that do not fluoresce such as eprinomectin, moxidectin, and ivermectin, are usually converted to fluorescent derivatives prior to their injection into the liquid chromatographic analytical column. The derivatization procedure commonly applied for this group of compounds includes reaction with trifluoroacetic anhydride in presence of A-methylimidazole as a base catalyst in acetonitrile (346, 347, 351, 352, 366, 369, 372-374). The formation of the fluorophore is achieved in 30 s at 25 C and results in a very stable derivative of ivermectin and moxidectin (353) but a relatively unstable derivative of eprinomectin (365). However, the derivatized extracts are not pure enough, so that their injection dramatically shortens the life of the liquid chromatographic column unless a silica solid-phase extraction cleanup is finally applied. 

When the dihydro-1,2,4-triazinone (194) is heated at 180 °C under reducing conditions there is rupture of the 1,2-bond followed by ring closure, producing 4,5-diphenyl-imidazolinone (195). Such reductive ring closures of benzotriazine 1-oxides (196) can give benzimidazoles, in particular 2-(4-thiazolyl)benzimidazoles (197) ( thiabendazole ). Similar reactions take place with 1,3,5-triazines. In fact, primary amines cleave the compounds completely with evolution of ammonia and formation of iV.iV -disubstituted formamidines. With suitable primary amines, though, this reaction can be designed to produce imidazolines or benzimidazoles (Scheme 113). 

Like mebendazole and albendazole, thiabendazole disrupts the assembly of microtubules. This results in the formation of aberrant spindles and disrupts cellular replication. 

Mechanisms The mechanism of action of albendazole is unclear. The drug blocks glucose uptake in both larval and adult parasites, which leads to decreased formation of ATP and subsequent parasite immobilization. The actions of albendazole may also include inhibition of microtubule assembly, as has been described for mebendazole and thiabendazole. 

Mizutani T, Yoshida K, Kawazoe S. Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products. Drug Metab Dispos 1994 22(5) 750-755. 

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