Identification and elucidation of the structure of in vivo metabolites of diaveridine in chicken

Wang, Hui; Yuan, Bo; Zeng, Zhenling; He, Lili; Ding, Huanzhong; Guo, Chunna; Kong, Xianming; Wang, Wei; Huang, Xianhui

doi:10.1016/j.jchromb.2014.06.010

Cited by 17 publications

(10 citation statements)

References 13 publications

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“…We propose in the light of the these former studies that the liver is the main metabolic organ of ADP. In contrast to TMP, diaveridine, and brodimoprim, O-demethylation were the major metabolic pathways in laboratory rats, target species, and humans 21 25 26 27 28 29 . If the phenyl moiety is important for the affinity of the drug to the O-demethylating enzyme, then the presence of a dimethylamino group may induce steric hindrance for this enzyme, resulting in the markedly different profiles in the major metabolic pathway.…”

Section: Discussionmentioning

confidence: 92%

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

Wang

Huang

Pan

et al. 2016

Sci Rep

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Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, α-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue.

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Section: Discussionmentioning

confidence: 92%

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

Wang

Huang

Pan

et al. 2016

Sci Rep

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“…In pig microsomes, six metabolites of DVD involving O-demethylation, α-hydroxylation, and N-oxidation were characterized using high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry ( 11 ). In chicken, 14 metabolites of DVD involving O-demethylation, α-hydroxylation, benzene ring-hydroxylation, N-oxidation, 4′-methylation, NH 2 -glucuronidation O-demethylation-glucuronidation, and N-oxidation glucuronidation were identified in the plasma after a single oral administration of DVD by high-performance liquid chromatography linear ion trap orbitrap (LC-LTQ-Orbitrap) ( 12 ). Although mass spectrometry is well known as a method for powerful structural elucidation of drug metabolites ( 13 ), owing to the complexity of a biological sample matrix, false negative or positive results are often observed because characterization of metabolites by mass spectrometry relies only on the ion information.…”

Section: Introductionmentioning

confidence: 99%

Metabolite Identification and Pharmacokinetic Behavior of Diaveridine in the Plasma of Pigs and Chickens Based on Radioactive Tracing Coupled With LC/MS-IT-TOF Assay

et al. 2022

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Diaveridine (DVD) is widely used for the prevention and treatment of coccidiosis and leucocytozoonosis infections in food-producing animals. To gain a better understanding of DVD metabolism and pharmacokinetics in healthy Landrace/Doric Cross castrated male pigs and both female and male Cobb 500 broiler chickens, a method involving radioactive tracing coupled with LC/MS-IT-TOF was developed for the identification and quantitation of DVD and its metabolites in pig and chicken plasma, and then was applied to investigate DVD pharmacokinetics. A simple MCX solid phase extraction procedure was adopted for sample preparation. After a single oral administration of 3H-DVD (10 mg/kg BW), three radioactive compounds (D0: DVD; D1: 3′-desmethyl-DVD; and D2: monoglucuronide of 3′-desmethyl-DVD) were identified in pig plasma, while only two radioactive compounds (D0 and D2) were identified in chicken plasma. In both species, the Cmax values for all detected compounds were reached at 2 h after dosing. The Cmax order was D2 (1.38 μg/ml) > D0 (0.49 μg/ml) > D1 (0.24 μg/ml) in pigs and D0 (1.55 μg/ml) > D2 (0.27 μg/ml) in chickens. The longer t1/2 (elimination half-life) of D0 contributed to the slow elimination of DVD-related compounds. The t1/2β of D0 in pigs (66.41 h) was significantly longer than that in chickens (48.30 h), but the t1/2 of total DVD-related metabolites in pigs (42.86 h) was lower than that in chickens (56.11 h). These findings suggested that the metabolism and pharmacokinetics of DVD in pigs and chickens were significantly different, and that this would affect its effectiveness, toxicology, and food safety in these animals.

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“…Diaveridine was found to act as a strong antibacterial drug due in part to two methoxy groups substituted on the benzene rings [4], in addition to the presence of two aromatic amino groups or the acidic hydrogen in the molecules make it acts as a strong acceptor [5,6]. It has wide antibacterial activity against many Gram-negative and Gram-positive bacteria [7]. It also has remarkable activity against coccidian so; it is used in the treatment of chicken coccidiosis, fowl cholera, and pullorum [8].…”

Section: Introductionmentioning

confidence: 99%

Spectrophotometric Studies on the Reaction of Diaveridine with Some Sulfonphthalein Dyes Based on Ion-Pair/Ion-Associate Complexes Formation

El-Ansary

Abdel-Kader

Asran

2018

Journal of Spectroscopy

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The ion-associate complexes of diaveridine were prepared in a solution and studied spectrophotometrically. The bulky counter anions such as sulfonphthalein acidic dyes, namely, bromocresol green (I), bromophenol blue (II), bromothymol blue (III), bromocresol purple (IV), bromocresol blue (V), o-cresol red (VI), p-cresol blue (VII), and m-cresol purple (VIII) were used for ion-associate complexes formation. The optimal characteristics for the color formation and the stoichiometry of the reaction were evaluated. Spectral characteristics and stability constants of the formed ion associates are discussed in terms of nature of donor and acceptor molecular structures. The molar absorptivities and association constants for the colored complexes were evaluated using the Benesi-Hildbrand equation. Conformity to Beer’s law enabled the assay of dosage form of the drug. The molar absorptivity, specific absorptivity, Sandell sensitivity, correlation coefficient, and detection and quantification limits were also calculated. The methods were validated in terms of accuracy, specificity, precision, and linearity. Also, spectrophotometric determination of the drug in pure and pharmaceutical preparations was tested.

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Identification and elucidation of the structure of in vivo metabolites of diaveridine in chicken

Cited by 17 publications

References 13 publications

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

Metabolite Identification and Pharmacokinetic Behavior of Diaveridine in the Plasma of Pigs and Chickens Based on Radioactive Tracing Coupled With LC/MS-IT-TOF Assay

Spectrophotometric Studies on the Reaction of Diaveridine with Some Sulfonphthalein Dyes Based on Ion-Pair/Ion-Associate Complexes Formation

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