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Bianca Ryser - One of the best experts on this subject based on the ideXlab platform.

Jan Zmudzki - One of the best experts on this subject based on the ideXlab platform.

  • Rapid method for the determination of tranquilizers and a beta-blocker in porcine and bovine kidney by liquid chromatography with tandem mass spectrometry.
    Analytica chimica acta, 2008
    Co-Authors: Kamila Mitrowska, Andrzej Posyniak, Jan Zmudzki
    Abstract:

    A fast and simple liquid chromatography with tandem mass spectrometry method for detection and confirmation of tranquilizers (chlorpromazine, propionylpromazine, acepromazine, triflupromazine, promazine, azaperone and its metabolite, azaperol) and beta-blocker (Carazolol) in porcine and bovine kidney has been presented. The method relies on the extraction with acetonitrile followed by centrifugation. After evaporation of acetonitrile, the residue was reconstituted in a mobile phase and filtrated. The separation of analytes was performed on a C18 column using a mobile phase of acetonitrile and ammonium formate buffer (0.05 M, pH 4.5) with gradient elution. The electrospray ionization was used to obtain the protonated molecules [M+H](+) and two product ions were monitored for each compound. For quantification deutered internal standards were used. The whole method has been validated according to the European Union requirements. Specificity, decision limit (CCalpha), detection capability (CCbeta), trueness and precision were determined. The results showed good trueness ranged from 73.2% to 110.6% with a good R.S.D., less than 13.0% under within-laboratory reproducibility conditions. The calculated critical concentrations of CCalpha for phenothiazines were between 5.8 and 6.6 microgkg(-1) while for azaperone CCalpha was 105.5 microgkg(-1) and for azaperol was 121.4 microgkg(-1). CCalpha for Carazolol was 16.7 microgkg(-1) in bovine and 21.9 microgkg(-1) in porcine kidney. CCbeta for phenothiazines were between 6.3 and 7.6 microgkg(-1), for azaperone was 119.0 microgkg(-1) and for azaperol was 140.0 microgkg(-1). For Carazolol in bovine kidney CCbeta was 18.6 microgkg(-1) whereas in porcine kidney was 24.4 microgkg(-1).

  • Rapid method for the determination of tranquilizers and a beta-blocker in porcine and bovine kidney by liquid chromatography with tandem mass spectrometry.
    Analytica Chimica Acta, 2008
    Co-Authors: Kamila Mitrowska, Andrzej Posyniak, Jan Zmudzki
    Abstract:

    Abstract A fast and simple liquid chromatography with tandem mass spectrometry method for detection and confirmation of tranquilizers (chlorpromazine, propionylpromazine, acepromazine, triflupromazine, promazine, azaperone and its metabolite, azaperol) and beta-blocker (Carazolol) in porcine and bovine kidney has been presented. The method relies on the extraction with acetonitrile followed by centrifugation. After evaporation of acetonitrile, the residue was reconstituted in a mobile phase and filtrated. The separation of analytes was performed on a C18 column using a mobile phase of acetonitrile and ammonium formate buffer (0.05 M, pH 4.5) with gradient elution. The electrospray ionization was used to obtain the protonated molecules [M+H] + and two product ions were monitored for each compound. For quantification deutered internal standards were used. The whole method has been validated according to the European Union requirements. Specificity, decision limit (CCα), detection capability (CCβ), trueness and precision were determined. The results showed good trueness ranged from 73.2% to 110.6% with a good R.S.D., less than 13.0% under within-laboratory reproducibility conditions. The calculated critical concentrations of CCα for phenothiazines were between 5.8 and 6.6 μg kg −1 while for azaperone CCα was 105.5 μg kg −1 and for azaperol was 121.4 μg kg −1 . CCα for Carazolol was 16.7 μg kg −1 in bovine and 21.9 μg kg −1 in porcine kidney. CCβ for phenothiazines were between 6.3 and 7.6 μg kg −1 , for azaperone was 119.0 μg kg −1 and for azaperol was 140.0 μg kg −1 . For Carazolol in bovine kidney CCβ was 18.6 μg kg −1 whereas in porcine kidney was 24.4 μg kg −1 .

Ginkel La Van - One of the best experts on this subject based on the ideXlab platform.

  • Surveillance 1994 into the occurrence of residues of beta-agonists, gestagens and tranquillizers in slaughter animals
    2012
    Co-Authors: Stolker Aam, Rossum Hj Van, Schwillens Plwj, Ginkel La Van
    Abstract:

    Gedurende het in 1994 uitgevoerde bewakingsonderzoek 'bijzondere slachtplaatsen' werden 196 monsters lever en 147 monsters urine onderzocht op de aanwezigheid van residuen van beta-agonisten, 197 monsters niervet werden onderzocht op de aanwezigheid van gestagenen en 141 monsters nier onderzocht op de aanwezigheid van tranquillizers. In geen van de onderzochte monsters urine en lever werden beta-agonisten aangetoond.Van de onderzochte monsters niervet werd in een geval het gestageen medroxyprogesteron(acetaat) aangetroffen, in alle overige onderzochte monsters niervet werden geen gestagenen aangetoond. Van de onderzochte monsters nier zijn in acht gevallen residuen van tranquillizers of Carazolol aangetroffen. Acepromazine was de meest voorko-mende tranquillizer, azaperol/a-zaperon en xylazine werden eenmaal aangetroffen. In een geval werd de beta-blokker Carazolol aangetroffen. Op basis van de resultaten is geadviseerd om in 1995 het onderzoek op beta-agonisten voort te zetten maar een andere matrix, namelijk retina te onderzoeken. Dit vanwege het feit dat de halfwaardetijd van beta-agonisten in retina langer is dan voor urine en lever. Het onderzoek op gestagenen en tranquillizers dient te worden voortgezet. Tevens werd aanbevolen om de aandacht in 1995 meer te richten op de anabole steroiden m.n. boldenon, methylboldenon, methyltestosteron en chloortestosteronacetaat.During the surveillance conducted in 1994, focussing on special slaughter places, 196 samples of liver and 147 samples of urine were analysed for the presence of residues of beta-agonists, 197 samples of kidney fat were analysed for the presence of gestagens and 141 samples of kidney were analysed for the presence of tranquillizers. In none of the analysed samples of urine and liver beta-agonists were detected. In one sample of kidney fat medroxyprogesterone (acetate) was detected. In 8 of the analysed samples of kidney residues of tranquillizers or Carazolol were detected. Acepromazine was the most frequently detected tranquillizer, azaperol/azaperone and xylazine were detected once. The beta-blocker carazalol also was detected once. Based on the results for beta-agonists it is suggested to continue the study using a matrix with a larger withdrawal time for residues, e.g. retina. Furthermore it is advised to continue the surveillance for gestagens and tranquillizers, and to focus the surveillance in 1995 on the anabolic steroids e.g. boldenone, methylboldenone, methyltestosterone and chlorotestosterone acetate.V

  • The detection and occurence of veterinary tranquillizers and the beta-blocker Carazolol in slaughter pigs
    2012
    Co-Authors: Ginkel La Van, Schwillens Plwj
    Abstract:

    Om binnen Nederland tot een analytisch onderzoeksmodel voor het opsporen van residuen van veterinaire tranquillizers alsmede de beta-blokker Carazolol te komen werd een analysemethode voor het onderzoek van monsters varkensnier ontwikkeld. De methode is gebaseerd op hogedruk vloeistofchromatografie met UV-spectrum identificatie. Extra identificatie kan, indien gewenst, met behulp van dunnelaagchromatografie plaatsvinden. De identificatiegrenzen varieren van minder dan 1 tot 2,5 mug/kg afhankelijk van het residu. In samenwerking met het Rijkskwaliteitsinstituut voor Land- en Tuinbouwprodukten werd een onderzoek uitgevoerd bij Nederlandse slachtvarkens. Een eerste onderzoek werd door het RIKILT uitgevoerd, verdachte en positieve monsters werden tevens door het RIVM onderzocht. Geconcludeerd wordt dat in 2,6% van de Nederlandse slachtvarkens residuen van tranquillizers of Carazolol aanwezig zijn en wel in 2,0% azepromazine, 0,2% azaperol/azaperon, 0,2 Carazolol en 0,2% azepromazine gecombineerd met Carazolol. Haloperidol, xylazine, propiopromazine en chloorpromazine werden bij dit bewakingsonderzoek niet aangetoond.Abstract not availableVH

  • Bewakingsonderzoek 1994 naar het voorkomen van residuen van beta-agonisten, gestagenen en tranquillizers in slachtdieren
    1996
    Co-Authors: Stolker Aam, Rossum Hj Van, Schwillens Plwj, Ginkel La Van
    Abstract:

    Gedurende het in 1994 uitgevoerde bewakingsonderzoek 'bijzondere slachtplaatsen' werden 196 monsters lever en 147 monsters urine onderzocht op de aanwezigheid van residuen van beta-agonisten, 197 monsters niervet werden onderzocht op de aanwezigheid van gestagenen en 141 monsters nier onderzocht op de aanwezigheid van tranquillizers. In geen van de onderzochte monsters urine en lever werden beta-agonisten aangetoond.Van de onderzochte monsters niervet werd in een geval het gestageen medroxyprogesteron(acetaat) aangetroffen, in alle overige onderzochte monsters niervet werden geen gestagenen aangetoond. Van de onderzochte monsters nier zijn in acht gevallen residuen van tranquillizers of Carazolol aangetroffen. Acepromazine was de meest voorko-mende tranquillizer, azaperol/a-zaperon en xylazine werden eenmaal aangetroffen. In een geval werd de beta-blokker Carazolol aangetroffen. Op basis van de resultaten is geadviseerd om in 1995 het onderzoek op beta-agonisten voort te zetten maar een andere matrix, namelijk retina te onderzoeken. Dit vanwege het feit dat de halfwaardetijd van beta-agonisten in retina langer is dan voor urine en lever. Het onderzoek op gestagenen en tranquillizers dient te worden voortgezet. Tevens werd aanbevolen om de aandacht in 1995 meer te richten op de anabole steroiden m.n. boldenon, methylboldenon, methyltestosteron en chloortestosteronacetaat.

Ruben Abagyan - One of the best experts on this subject based on the ideXlab platform.

  • analysis of full and partial agonists binding to β2 adrenergic receptor suggests a role of transmembrane helix v in agonist specific conformational changes
    Journal of Molecular Recognition, 2009
    Co-Authors: Vsevolod Katritch, Michael A. Hanson, Vadim Cherezov, Kimberly A Reynolds, Christopher B Roth, Mark Yeager, Ruben Abagyan
    Abstract:

    The 2.4 A crystal structure of the β2-adrenergic receptor (β2AR) in complex with the high-affinity inverse agonist (-)-Carazolol provides a detailed structural framework for the analysis of ligand recognition by adrenergic receptors. Insights into agonist binding and the corresponding conformational changes triggering GPCR activation mechanism are of special interest. Here we show that while the Carazolol pocket captured in the β2AR crystal structure accommodates (-)-isoproterenol and other agonists without steric clashes, a finite movement of the flexible extracellular part of TMV helix (TM-Ve) obtained by receptor optimization in the presence of docked ligand can further improve the calculated binding affinities for agonist compounds. Tilting of TM-Ve towards the receptor axis provides a more complete description of polar receptor/ligand interactions for full and partial agonists, by enabling optimal engagement of agonists with two experimentally identified anchor sites, formed by Asp113/Asn312 and Ser203/Ser204/Ser207 side chains. Further, receptor models incorporating a flexible TM-V backbone allow reliable prediction of binding affinities for a set of diverse ligands, suggesting potential utility of this approach to design of effective and subtypespecific agonists for adrenergic receptors. Systematic differences in capacity of partial, full and inverse agonists to induce TM-V helix tilt in the β2AR model suggest potential role of TM-V as a conformational “rheostat” involved in the whole spectrum of β2AR responses to small molecule signals.

  • Analysis of full and partial agonists binding to β2‐adrenergic receptor suggests a role of transmembrane helix V in agonist‐specific conformational changes
    Journal of molecular recognition : JMR, 2009
    Co-Authors: Vsevolod Katritch, Michael A. Hanson, Vadim Cherezov, Kimberly A Reynolds, Christopher B Roth, Mark Yeager, Ruben Abagyan
    Abstract:

    The 2.4 A crystal structure of the β2-adrenergic receptor (β2AR) in complex with the high-affinity inverse agonist (-)-Carazolol provides a detailed structural framework for the analysis of ligand recognition by adrenergic receptors. Insights into agonist binding and the corresponding conformational changes triggering GPCR activation mechanism are of special interest. Here we show that while the Carazolol pocket captured in the β2AR crystal structure accommodates (-)-isoproterenol and other agonists without steric clashes, a finite movement of the flexible extracellular part of TMV helix (TM-Ve) obtained by receptor optimization in the presence of docked ligand can further improve the calculated binding affinities for agonist compounds. Tilting of TM-Ve towards the receptor axis provides a more complete description of polar receptor/ligand interactions for full and partial agonists, by enabling optimal engagement of agonists with two experimentally identified anchor sites, formed by Asp113/Asn312 and Ser203/Ser204/Ser207 side chains. Further, receptor models incorporating a flexible TM-V backbone allow reliable prediction of binding affinities for a set of diverse ligands, suggesting potential utility of this approach to design of effective and subtypespecific agonists for adrenergic receptors. Systematic differences in capacity of partial, full and inverse agonists to induce TM-V helix tilt in the β2AR model suggest potential role of TM-V as a conformational “rheostat” involved in the whole spectrum of β2AR responses to small molecule signals.

Christopher T Elliott - One of the best experts on this subject based on the ideXlab platform.

  • development of a rapid screening test for veterinary sedatives and the beta blocker Carazolol in porcine kidney by elisa
    Analyst, 2004
    Co-Authors: John Cooper, Phillippe Delahaut, Terence L Fodey, Christopher T Elliott
    Abstract:

    Sedatives and tranquillisers are frequently used to reduce stress during the transportation of food producing animals. The most widely used classes of sedatives include the butyrophenone azaperone, the phenothiazines acepromazine, propionylpromazine, chlorpromazine and the [small beta]-blocker, Carazolol. For regulatory control purposes, tolerances for azaperone and Carazolol have been set by the European Union as 100 and 25 [micro sign]g kg(-1), respectively. Furthermore, the use of the phenothiazines is prohibited and therefore has a zero tolerance. A method for the detection of residues of five tranquillisers and one [small beta]-blocker using a single ELISA plate has been developed. Kidney samples (2.5 g) were extracted with dichloromethane and applied to a competitive enzyme immunoassay using three polyclonal antibodies raised in rabbits against azaperol, propionylpromazine and Carazolol conjugates. In sample matrix, the azaperol antibody cross-reacted 28.0% with azaperone and the propionylpromazine antibody cross-reacted 24.9% with acepromazine and 11.7% with chlorpromazine. In the ELISA, the detection capabilities of the six sedatives, azaperol, azaperone, Carazolol, acepromazine, chlorpromazine, and propionylpromazine are 5, 15, 5, 5, 20 and 5 [micro sign]g kg(-1), respectively. The proposed method is a sensitive and rapid multi-residue technique that offers a cost effective alternative to current published procedures, without any concession on the ability to detect sedative misuse.

  • Determination of Carazolol residues in porcine tissue by radioreceptor assay
    Analytica Chimica Acta, 2002
    Co-Authors: Susanne A. Meenagh, J. D. G. Mcevoy, Christopher T Elliott
    Abstract:

    A radioreceptor assay was developed for the determination of the -blocker Carazolol in porcine muscle and kidney. The method involves a simple alkaline extraction procedure using diethyl ether followed by a competitive assay between Carazolol residues and [ 3 H]-dihydroalprenolol ([ 3 H]-DHA) using solubilised2-adrenoceptors isolated from a transfected cell line. The limit of detection (LOD) was determined using 20 reference blank samples of pig kidney and pig muscle. LODs for muscle (0.93 gk g −1 ) and kidney (1.47 gk g −1 ) were well below their respective European community maximum residue limits, (MRLs 5 and 25 gk g −1 , respectively). The assay was used to investigate if Carazolol residues persisted in pig tissues for up to 30 h post-intramuscular injection at the recommended dose rate (10g Carazolol/kg body weight). The highest mean±S.D. concentrations were detected at 1 h post-injection in kidney (10.84 ± 1.3 gk g −1 ) and muscle (3.59 ± 0.2 gk g −1 ) which were less than the respective MRLs. It is concluded that this method offers a robust and rapid alternative to other methods for the screening of Carazolol residues in pig meat. © 2002 Elsevier Science B.V. All rights reserved.