Albendazole detection

In ruminants, oral doses of albendazole are readily absorbed from the gut. Following absorption, albendazole undergoes extensive metabolism by rapid first-pass oxidation of its sulfoxide group to form albendazole sulfoxide, then further oxidation to form albendazole sulfone, and by deacetylation of the carbamate group to form albendazole-2-aminosulfone. Albendazole sulfoxide, albendazole sulfone, and albendazole-2-aminosulfone are the main metabolites found in tissues, whereas other minor metabolites have been also detected at much lower concentrations. 

After subcutaneous or intramuscular injection of netobimin into cattle, absorption was rapid but plasma levels of radioactivity were lower than those achieved following oral administration. This indicates that absorption occurred prior to the conversion to albendazole since high levels of parent drug were found in plasma and milk soon after the injection. On the other hand, at 12 h after the injection the parent drug could not be detected at the injection site or in liver. 

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. 

Fig. 29.10.1 Typical chromatograms of a mixed standard working solution (A), a control milk sample (B), and a control milk sample fortified with benzimidazoles at concentrations close to their detection limits (C). Peaks 1, albendazole-2-aminosulfone 2, albendazole sulfoxide 3, oxibendazole 4, oxfendazole 5, albendazole sulfone 6, p-hydroxyfenbendazole 7, albendazole 8, mebendazole 9, fenbendazole sulfone 10, fenbendazole. (From Ref. 343.).

Liver samples from cattle (292) and pigs (394) were found to be free of any detectable residues of these compounds. Of the 529 sheep liver samples analysed only one was found to have detectable residues (3,500/xg/kg, albendazole) which are significantly above the MRL for this compound (1000/xg/kg). 

Sensitive and selective fluorescent IPC detection was recently used to analyze underivatized amino acids [19], albendazole marker residue in animal tissues [20], loratidine [21], early synthetic dyes [22], bitter orange alkaloids [23], and ochratoxin A in red wines [24]. 

Plasma. Albendazole (ABZ), albendazole-sulfone (ABZ-S02), albendazole 2-aminosulfone (ABZ-NH2, marker metabolite) and albendazole-sulfoxide (ABZ-SO), were extracted from the plasma using a perchloric acid precipitation method followed by a solid phase extraction procedure. The residue levels were quantitated using a normal or reversed phase HPLC method with fluorescence detection. 

Albendazole is variably absorbed after oral administration. A fatty meal enhances absorption. After a 400-mg oral dose, albendazole cannot be detected in plasma, because the drug is rapidly metabolized in the liver to its sulfoxide, which has potent anthelmintic activity. Both the (-t-) and (-) enantiomers of albendazole sulfoxide are formed the (-t-) enantiomer reaches much higher peak plasma concentrations and is cleared much more slowly. Albendazole sulfoxide is -70% bound to plasma proteins and has a variable plasma tj (-4-15 hours). It is well distributed into various tissues including hydatid cysts, probably explaining its greater efficacy for tissue-dwelling helminths. Formation of albendazole sulfoxide is catalyzed by both microsomal flavin monooxygenase and CYP isoforms in the liver. Albendazole metabolites are excreted mainly in the urine. 

Stolker et al. " described an analytical method based on TFC-LC-MS/MS for the direct analysis of 11 veterinary drugs (belonging to seven different classes) in milk. The method was applied to a series of raw milk samples, and the analysis was carried out for albendazole, difloxacin, tetracycline, oxytetracycline, phenylbutazone, salinomycin-Na, spiramycin, and sulfamethazine in milk samples with various fat contents. Even without internal standards, results proved to be linear and quantitative in the concentration range of 50-500 (xg/1, as well as repeatable (RSD<14% sulfamethazine and difloxacin <20%). The limits of detection were between 0.1 and 5.2 xg/l, far below the maximum residue limits for milk set by the EU. While matrix effects, namely, ion suppression or enhancement, were observed for all the analytes, the method proved to be useful for screening purposes because of its detection limits, linearity, and repeatability. A set of blank and fortified raw milk samples was analyzed and no false-positive or falsenegative results were obtained. 

In one study albendazole 15 mg/kg daily in three divided doses was given to 8 patients with eystieereosis. The plasma levels of the active metabolite of albendazole (albendazole sulfoxide) were found to be increased by about 50% by the use of dexamethasone 8 mg every 8 hours. Another study did not detect significantly increased maximum plasma levels of albendazole sulfoxide, when dexamethasone was given, but the AUC was increased twofold, and there was a decrease in its clearance. ... 

Anthelmintics The major classes of anthelmintics, or antiparasitic drugs, are benzimidazoles and mac-rocyclic lactones (avermectins and milbemycins). USDA/FSIS have approved a method based on LC/ fluorescence detection for determination of the anthelmintics albendazole and ivermectin in tissues (albendazole extracted with ethyl acetate and cleanup... 

Schwab AE, Boakye DA, Kyelem D, Prichard RK. Detection of benzimidazole resistance-associated mutations in the filarial nematode Wuch-ereria h(mcrofti and evidence for selection by albendazole and ivermectin combination treatment. Am J Trop Med Hyg 2005 73 234-8. Diawara A, Schwenkenbecher JM, Kaplan RM, Prichard RK. Molecular and biological diagnostic tests for monitoring benzimidazole resistance in human soil-transmitted helminths. Am J Trop Med Hyg 2013 88(6) 1052-61. 

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