The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Bertrand Rochat - One of the best experts on this subject based on the ideXlab platform.
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comparison between a high resolution single stage orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs
Rapid Communications in Mass Spectrometry, 2012Co-Authors: Hugues Henry, Hamid Reza Sobhi, Olaf Scheibner, Maciej Bromirski, Subodh B Nimkar, Bertrand RochatAbstract:The capabilities of a high-resolution (HR), accurate mass spectrometer (Exactive-MS) operating in full scan MS mode was investigated for the quantitative LC/MS analysis of drugs in patients' plasma samples. A mass resolution of 50 000 (FWHM) at m/z 200 and a mass extracted window of 5 ppm around the theoretical m/z of each analyte were used to construct chromatograms for quantitation. The quantitative performance of the Exactive-MS was compared with that of a triple quadrupole mass spectrometer (TQ-MS), TSQ Quantum Discovery or Quantum Ultra, operating in the conventional selected reaction monitoring (SRM) mode. The study consisted of 17 therapeutic drugs including 8 antifungal agents (anidulafungin, caspofungin, fluconazole, itraconazole, Hydroxyitraconazole posaconazole, voriconazole and voriconazole-N-oxide), 4 immunosuppressants (ciclosporine, everolimus, sirolimus and tacrolimus) and 5 protein kinase inhibitors (dasatinib, imatinib, nilotinib, sorafenib and sunitinib). The quantitative results obtained with HR-MS acquisition show comparable detection specificity, assay precision, accuracy, linearity and sensitivity to SRM acquisition. Importantly, HR-MS offers several benefits over TQ-MS technology: absence of SRM optimization, time saving when changing the analysis from one MS to another, more complete information of what is in the samples and easier troubleshooting. Our work demonstrates that U/HPLC coupled to Exactive HR-MS delivers comparable results to TQ-MS in routine quantitative drug analyses. Considering the advantages of HR-MS, these results suggest that, in the near future, there should be a shift in how routine quantitative analyses of small molecules, particularly for therapeutic drugs, are performed. Copyright © 2012 John Wiley & Sons, Ltd.
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofu
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole- N -oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofungin
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.
Oscar Marchetti - One of the best experts on this subject based on the ideXlab platform.
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofu
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole- N -oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofungin
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.
Laurent A. Decosterd - One of the best experts on this subject based on the ideXlab platform.
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofu
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole- N -oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofungin
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.
Guy Van Den Mooter - One of the best experts on this subject based on the ideXlab platform.
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clinical study of solid dispersions of itraconazole prepared by hot stage extrusion
European Journal of Pharmaceutical Sciences, 2005Co-Authors: Tinne Daems, Jan De Hoon, Anne Van Hecken, Marleen Depre, Mariepaule Bouche, Paul Prinsen, Geert Verreck, Jef Peeters, Marcus E Brewster, Guy Van Den MooterAbstract:Abstract The aim of this study was to investigate the performance of three new solid dispersion formulations of itraconazole in human volunteers in comparison with Sporanox®, the marketed form. Solid dispersions made up of itraconazole (40%, w/w) and HPMC 2910, Eudragit E100 or a mixture of Eudragit E100-PVPVA64 were manufactured by hot-stage extrusion and filled in gelatin capsules. The formulations were tested in eight human volunteers in a double blind, single dose, and cross-over study. Concentrations of the drug and its metabolite Hydroxyitraconazole in the plasma were determined using HPLC. The in vivo performance was evaluated by comparing the mean area under the plasma concentration–time curves (AUC), the mean maximum plasma concentration (Cmax), and the mean time to reach Cmax (Tmax). The mean bioavailability of itraconazole was comparable after administration of the HPMC solid dispersion, compared to Sporanox®, while it was lower after administration of the Eudragit E100 or Eudragit E100-PVPVA64 dispersions. Due to high variability, a significant decrease in AUC and Cmax was only observed for the Eudragit E100-PVPVA formulation. Although the solid dispersions showed different in vitro dissolution behaviour, Tmax values were comparable. The same observations with respect to AUC, Cmax and Tmax could be made for Hydroxyitraconazole. The present results indicate that hot-stage extrusion can be considered as a valuable alternative for manufacturing solid dispersions of itraconazole.
Thomas Mercier - One of the best experts on this subject based on the ideXlab platform.
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofu
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole- N -oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (
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multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole Hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofungin
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A. Decosterd, Benoit Pesse, Boris Zanolari, Thierry Calandra, Thomas Mercier, Nicolas Widmer, Bertrand Rochat, F. Tissot, Jacques Bille, Oscar MarchettiAbstract:Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, Hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.
