The Experts below are selected from a list of 1164 Experts worldwide ranked by ideXlab platform
Yiu Tung Wong - One of the best experts on this subject based on the ideXlab platform.
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determination of Closantel and rafoxanide in animal tissues by online anionic mixed mode solid phase extraction followed by isotope dilution liquid chromatography tandem mass spectrometry
IEEE Journal of Solid-state Circuits, 2011Co-Authors: Shirley Sauling Lai, Hoi Sze Yeung, Wai O Lee, Yiu Tung WongAbstract:A rapid and high-throughput isotope dilution LC-MS/MS method with online sample pre-concentration and clean-up using anionic mixed-mode SPE was described for the determination of Closantel and rafoxanide in edible bovine and ovine tissues. Tissue samples were extracted with acetonitrile and acetone mixture (60:40, v/v). Sample pre-concentration, clean-up and analysis were completed simultaneously with the online MAX SPE LC-MS/MS system. Closantel-(13) C(6) and rafoxanide-(13) C(6) were used as the internal standards to improve the precision of the method. The method was validated with edible ovine and bovine tissues (muscle, kidney and liver) fortified at three different levels. The accuracy and RSD were 86-106% and ≤14%, respectively. This high-throughput method was suitable for routine quantitative analysis of Closantel and rafoxanide in food safety surveillance samples.
Kim D. Janda - One of the best experts on this subject based on the ideXlab platform.
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Dual Protonophore–Chitinase Inhibitors Dramatically Affect O. volvulus Molting
2015Co-Authors: Major Gooyit, Nancy Tricoche, Sara Lustigman, Kim D. JandaAbstract:The L3-stage-specific chitinase OvCHT1 has been implicated in the development of Onchocerca volvulus, the causative agent of onchocerciasis. Closantel, a known anthelmintic drug, was previously discovered as a potent and specific OvCHT1 inhibitor. As Closantel is also a known protonophore, we performed a simple scaffold modulation to map out the structural features that are relevant for its individual or dual biochemical roles. Furthermore, we present that either OvCHT1 inhibition or protonophoric activity was capable of affecting O. volvulus L3 molting and that the presence of both activities in a single molecule yielded more potent inhibition of the nematode’s developmental process
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design synthesis and biological activities of Closantel analogues structural promiscuity and its impact on onchocerca volvulus
Journal of Medicinal Chemistry, 2011Co-Authors: Amanda L. Garner, Christian Gloeckner, Nancy Tricoche, Sara Lustigman, Joseph S Zakhari, Moses Samje, Fidelis Chongwa, Kim D. JandaAbstract:Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, Closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, Closantel’s anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3 molting was investigated. Structure–activity relationship studies on an active Closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critic...
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repositioning of an existing drug for the neglected tropical disease onchocerciasis
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Christian Gloeckner, Fana B Mersha, Yelena Oksov, Nancy Tricoche, Lisa M Eubanks, Gunnar F Kaufmann, Sara Lustigman, Amanda L. Garner, Kim D. JandaAbstract:Onchocerciasis, or river blindness, is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus that affects more than 37 million people, mainly in third world countries. Currently, the only approved drug available for mass treatment is ivermectin, however, drug resistance is beginning to emerge, thus, new therapeutic targets and agents are desperately needed to treat and cure this devastating disease. Chitin metabolism plays a central role in invertebrate biology due to the critical structural function of chitin for the organism. Taken together with its absence in mammals, targeting chitin is an appealing therapeutic avenue. Importantly, the chitinase OvCHT1 from O. volvulus was recently discovered, however, its exact role in the worm’s metabolism remains unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a veterinary anthelmintic with known proton ionophore activities, was identified as a potent and specific inhibitor of filarial chitinases, an activity not previously reported for this compound. Notably, Closantel was found also to completely inhibit molting of O. volvulus infective L3 stage larvae. Closantel appears to target two important biochemical processes essential to filarial parasites. To begin to unravel Closantel’s effects, a retro-fragment-based study was used to define structural elements critical for Closantel’s chitinase inhibitor function. As resources towards the development of new agents that target neglected tropical diseases are scant, the finding of an existing drug with impact against O. volvulus provides promise in the hunt for new therapies against river blindness.
Shirley Sauling Lai - One of the best experts on this subject based on the ideXlab platform.
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determination of Closantel and rafoxanide in animal tissues by online anionic mixed mode solid phase extraction followed by isotope dilution liquid chromatography tandem mass spectrometry
IEEE Journal of Solid-state Circuits, 2011Co-Authors: Shirley Sauling Lai, Hoi Sze Yeung, Wai O Lee, Yiu Tung WongAbstract:A rapid and high-throughput isotope dilution LC-MS/MS method with online sample pre-concentration and clean-up using anionic mixed-mode SPE was described for the determination of Closantel and rafoxanide in edible bovine and ovine tissues. Tissue samples were extracted with acetonitrile and acetone mixture (60:40, v/v). Sample pre-concentration, clean-up and analysis were completed simultaneously with the online MAX SPE LC-MS/MS system. Closantel-(13) C(6) and rafoxanide-(13) C(6) were used as the internal standards to improve the precision of the method. The method was validated with edible ovine and bovine tissues (muscle, kidney and liver) fortified at three different levels. The accuracy and RSD were 86-106% and ≤14%, respectively. This high-throughput method was suitable for routine quantitative analysis of Closantel and rafoxanide in food safety surveillance samples.
Fengchi Wang - One of the best experts on this subject based on the ideXlab platform.
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Determination of Closantel residues in milk and animal tissues by HPLC with fluorescence detection and SPE with oasis MAX cartridges.
Journal of Chromatographic Science, 2008Co-Authors: Hanwen Sun, Fengchi WangAbstract:A liquid chromatographic method for the determination of Closantel residues in milk and tissues is developed and validated. An acetonitrile-acetone solution (80:20, v/v) is used for the extraction of Closantel residues from milk and animal tissues, and the extract is purified by solid-phase extraction with Oasis MAX cartridges and a mixture of formic acid-acetonitrile (5:95, v/v) as the elution solution. A C(18) bonded silica column is used for chromatographic separation. The mobile phase consists of acetonitrile-water (85:15, v/v) containing 0.05% triethylamine at pH 2.5, adjusted with phosphoric acid with the flow-rate set at 1.0 mL/min. Using the fluorescence emission of Closantel at lambda(ex) = 335 nm and lambda(ex) = 510 nm, the calibration curve is linear, with a correlation coefficient of 0.9999 over the concentration range of 10-5000 microg/kg for the tissue sample and 10-5000 microg/L for the milk sample. The detection limit (s/n = 3) is 3 microg/kg for tissue sample and 3 microg/L for milk sample. The intra- and inter-day repeatabilities are between 3.35-7.66% and 4.04-8.67%, respectively. The proposed method enables the quantitative determination of Closantel residues at levels as low as 10 microg/kg in animal tissue samples and 10 microg/L in milk samples.
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Validated method for determination of ultra-trace Closantel residues in bovine tissues and milk by solid-phase extraction and liquid chromatography-electrospray ionization-tandem mass spectrometry.
Journal of Chromatography A, 2007Co-Authors: Hanwen Sun, Fengchi WangAbstract:Abstract A liquid chromatographic–electrospray ionisation-tandem mass spectrometry method (LC–ESI-MS/MS) with solid extraction was developed and validated for the detection and determination of Closantel residues in bovine tissues and milk. An acetonitrile–acetone mixture (80:20, v/v) was used for one-stage extraction of Closantel residues in bovine tissues and milk samples, and the extract was cleaned by solid phase extraction with Oasis MAX cartridges. The mass spectrometer was operated in multiple reactions monitoring mode with negative electrospray interface. The limits of detection in different matrices were in the range of 0.008–0.009 μg/kg. The overall recoveries for bovine muscle, liver, kidney and milk samples spiked at four levels including MRL were in the range of 76.0–94.3%. The overall relative standard deviations were in the range of 3.57–8.61%. The linearity is satisfactory with a correlation coefficient ( r 2 ) of 0.9913–0.9987 at both concentration ranges of 0.02–100 μg/kg and 200–5000 μg/kg. The method is capable of identifying Closantel residues at ≥0.02 μg/kg levels and was applied in the determination of Closantel residues in animal origin foods.
Hoi Sze Yeung - One of the best experts on this subject based on the ideXlab platform.
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determination of Closantel and rafoxanide in animal tissues by online anionic mixed mode solid phase extraction followed by isotope dilution liquid chromatography tandem mass spectrometry
IEEE Journal of Solid-state Circuits, 2011Co-Authors: Shirley Sauling Lai, Hoi Sze Yeung, Wai O Lee, Yiu Tung WongAbstract:A rapid and high-throughput isotope dilution LC-MS/MS method with online sample pre-concentration and clean-up using anionic mixed-mode SPE was described for the determination of Closantel and rafoxanide in edible bovine and ovine tissues. Tissue samples were extracted with acetonitrile and acetone mixture (60:40, v/v). Sample pre-concentration, clean-up and analysis were completed simultaneously with the online MAX SPE LC-MS/MS system. Closantel-(13) C(6) and rafoxanide-(13) C(6) were used as the internal standards to improve the precision of the method. The method was validated with edible ovine and bovine tissues (muscle, kidney and liver) fortified at three different levels. The accuracy and RSD were 86-106% and ≤14%, respectively. This high-throughput method was suitable for routine quantitative analysis of Closantel and rafoxanide in food safety surveillance samples.