The Experts below are selected from a list of 54705 Experts worldwide ranked by ideXlab platform
Robert S Plumb - One of the best experts on this subject based on the ideXlab platform.
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development of a high sensitivity bioanalytical method for alprazolam using ultra performance liquid chromatography tandem mass spectrometry
Drug Testing and Analysis, 2010Co-Authors: Joanne Mather, Paul D Rainville, Warren B Potts, Norman W Smith, Robert S PlumbAbstract:A rapid, specific, assay was developed for the benzodiapine alprazolam in rat plasma using sub-2 µm particle liquid chromatography (LC) and tandem quadrupole mass spectrometry (MS/MS). The Limit of Quantification using protein precipitation was determined to 10 pg/mL, whereas the Limit of Quantification using solid-phase extraction (SPE) was determined to be 1.0 pg/mL. The assay was optimized for throughput and resolution of the analyte of interest from the hydroxy metabolite. During the method development process the plasma matrix signal was monitored, for lipids and other endogenous metabolites, to maximize signal response and minimize ion suppression. This was achieved by using a tandem quadrupole mass spectrometer equipped with a novel collision cell design which allowed for the simultaneous collection of full scan MS and multiple reaction monitoring (MRM) data. The lipid profile from the SPE process was significantly less than obtained with the protein precipitation approach. Copyright © 2010 John Wiley & Sons, Ltd.
Rosa Draisci - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatography with tandem mass spectrometry method for the determination of nicotine and minor tobacco alkaloids in electronic cigarette refill liquids and second hand generated aerosol
IEEE Journal of Solid-state Circuits, 2017Co-Authors: Marco Famele, Jolanda Palmisani, Carolina Ferranti, Carmelo Abenavoli, L Palleschi, Rosanna Mancinelli, Rosanna Maria Fidente, Gianluigi De Gennaro, Rosa DraisciAbstract:A liquid chromatography with tandem mass spectrometry method for the simultaneous Quantification of nicotine and seven minor tobacco alkaloids in both refill liquids for electronic cigarettes and their generated aerosol was developed and validated. The Limit of detection and Limit of Quantification values were 0.3–20.0 and 1.0–31.8 ng/mL, respectively. Within-laboratory reproducibility was 8.2–14.2% at Limit of Quantification values and 4.8–12.7 % at other concentration levels. Inter-day recovery was 75.8–116.4%. The method was applied to evaluate the compliance of commercial liquids (n = 95) with their labels and to assess levels of minor alkaloids. Levels of nicotine and its correlated compounds were also evaluated in generated aerosol. About 47% of samples showed differences above ± 10 % of the stated nicotine concentration. About 78% of the “zero nicotine” liquids showed traces in the range of 1.3 ± 0.1–254.0 ± 14.6 μg/mL. Nicotine-N'-oxides, myosmine, and anatabine were the most common minor alkaloids in liquids containing nicotine. Nicotine and N'-oxides were detected in all air samples when aerosol was generated from liquids containing nicotine. Nicotine average emissions from electronic cigarette (2.7 ± 0.9 μg/m3) were significantly lower (p < 0.01, t-Test) respect to conventional cigarette (30.2 ± 1.5 μg/m3). This article is protected by copyright. All rights reserved
Marco Famele - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatography with tandem mass spectrometry method for the determination of nicotine and minor tobacco alkaloids in electronic cigarette refill liquids and second hand generated aerosol
IEEE Journal of Solid-state Circuits, 2017Co-Authors: Marco Famele, Jolanda Palmisani, Carolina Ferranti, Carmelo Abenavoli, L Palleschi, Rosanna Mancinelli, Rosanna Maria Fidente, Gianluigi De Gennaro, Rosa DraisciAbstract:A liquid chromatography with tandem mass spectrometry method for the simultaneous Quantification of nicotine and seven minor tobacco alkaloids in both refill liquids for electronic cigarettes and their generated aerosol was developed and validated. The Limit of detection and Limit of Quantification values were 0.3–20.0 and 1.0–31.8 ng/mL, respectively. Within-laboratory reproducibility was 8.2–14.2% at Limit of Quantification values and 4.8–12.7 % at other concentration levels. Inter-day recovery was 75.8–116.4%. The method was applied to evaluate the compliance of commercial liquids (n = 95) with their labels and to assess levels of minor alkaloids. Levels of nicotine and its correlated compounds were also evaluated in generated aerosol. About 47% of samples showed differences above ± 10 % of the stated nicotine concentration. About 78% of the “zero nicotine” liquids showed traces in the range of 1.3 ± 0.1–254.0 ± 14.6 μg/mL. Nicotine-N'-oxides, myosmine, and anatabine were the most common minor alkaloids in liquids containing nicotine. Nicotine and N'-oxides were detected in all air samples when aerosol was generated from liquids containing nicotine. Nicotine average emissions from electronic cigarette (2.7 ± 0.9 μg/m3) were significantly lower (p < 0.01, t-Test) respect to conventional cigarette (30.2 ± 1.5 μg/m3). This article is protected by copyright. All rights reserved
Jos H Beijnen - One of the best experts on this subject based on the ideXlab platform.
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multiparameter flow cytometry assay for Quantification of immune cell subsets pd 1 expression levels and pd 1 receptor occupancy by nivolumab and pembrolizumab
Cytometry Part A, 2019Co-Authors: Dick Pluim, Willeke Ros, Iris H C Miedema, Jos H Beijnen, Jan H M SchellensAbstract:We report the development and validation of a 12 parameter immunofluorescence flow cytometry method for the sensitive determination of cell concentrations, their expression of PD-1, and PD-1 receptor occupancy. Cell subsets include CD4+ and CD8+ -T-cells, B-cells, natural killer cells, classical-, intermediate- and non-classical monocytes, and myeloid- and plasmacytoid dendritic cells. Cells were isolated from peripheral blood by density gradient centrifugation. The validation parameters included specificity, linearity, Limit of Quantification, precision, biological within- and between subject variations. The lower Limit of Quantification was 5.0% of PD-1+ cells. Samples were stable for at least 153 days of storage at -80°C. The clinical applicability of the method was demonstrated in 11 advanced cancer patients by the successful determination of immune cell concentrations, relative number of PD-1+ immune cells, and number of PD-1 molecules per immune cell. Shortly after infusion of nivolumab, receptor occupancy on CD8+ -T-cells was 98%. Similar values were found predose cycle 2, suggesting receptor occupancy remained high throughout the entire cycle. © 2019 International Society for Advancement of Cytometry.
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incorporation of concentration data below the Limit of Quantification in population pharmacokinetic analyses
Pharmacology Research & Perspectives, 2015Co-Authors: Jos H Beijnen, Jan H M Schellens, Ron J Keizer, Robert S Jansen, Hilde Rosing, Bas Thijssen, Alwin D R HuitemaAbstract:Handling of data below the lower Limit of Quantification (LLOQ), below the Limit of Quantification (BLOQ) in population pharmacokinetic (PopPK) analyses is important for reducing bias and imprecision in parameter estimation. We aimed to evaluate whether using the concentration data below the LLOQ has superior performance over several established methods. The performance of this approach (“All data”) was evaluated and compared to other methods: “Discard,” “LLOQ/2,” and “LIKE” (likelihood-based). An analytical and residual error model was constructed on the basis of in-house analytical method validations and analyses from literature, with additional included variability to account for model misspecification. Simulation analyses were performed for various levels of BLOQ, several structural PopPK models, and additional influences. Performance was evaluated by relative root mean squared error (RMSE), and run success for the various BLOQ approaches. Performance was also evaluated for a real PopPK data set. For all PopPK models and levels of censoring, RMSE values were lowest using “All data.” Performance of the “LIKE” method was better than the “LLOQ/2” or “Discard” method. Differences between all methods were small at the lowest level of BLOQ censoring. “LIKE” method resulted in low successful minimization (<50%) and covariance step success (<30%), although estimates were obtained in most runs (~90%). For the real PK data set (7.4% BLOQ), similar parameter estimates were obtained using all methods. Incorporation of BLOQ concentrations showed superior performance in terms of bias and precision over established BLOQ methods, and shown to be feasible in a real PopPK analysis.
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quantitative analysis of gemcitabine triphosphate in human peripheral blood mononuclear cells using weak anion exchange liquid chromatography coupled with tandem mass spectrometry
Journal of Mass Spectrometry, 2006Co-Authors: Stephan A Veltkamp, Jos H Beijnen, Jan H M Schellens, Robert S Jansen, Hilde Rosing, Michel J X Hillebrand, Enaksha R Wickremsinhe, E J PerkinsAbstract:Gemcitabine triphosphate (dFdCTP) is a highly active metabolite of gemcitabine. It is formed intra-cellularly via the phosphorylation of gemcitabine by deoxycytidine kinase. The monitoring of dFdCTP in human peripheral blood mononuclear cells (PBMCs), in addition to plasma concentrations of gemcitabine and its metabolite 2′,2′-difluorodeoxyuridine, is considered very useful in determining pharmacokinetic–pharmacodynamic relationships. We describe a novel sensitive assay for the Quantification of dFdCTP in human PBMCs. The method is based on weak anion-exchange liquid chromatography and detection with tandem mass spectrometry (LC-MS/MS). The assay has been validated from 1 ng/ml (lower Limit of Quantification, LLOQ) to 25 ng/ml (upper Limit of Quantification, ULOQ) using 180 µl aliquots of PBMC extracts containing ∼0.648 mg protein or 3.8 × 106 lysed PBMCs. The LLOQ is equivalent to 94 fmol/106 cells (1 ng/ml = 0.18 ng/180 µl or 0.18 ng/0.648 mg protein = 0.047 ng/106 cells or 94 fmol/106 cells). This highly sensitive assay is capable of quantifying about 200-fold lower concentrations of dFdCTP in human PBMCs than currently available methods. Copyright © 2006 John Wiley & Sons, Ltd.
Paul D Rainville - One of the best experts on this subject based on the ideXlab platform.
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development of a high sensitivity bioanalytical method for alprazolam using ultra performance liquid chromatography tandem mass spectrometry
Drug Testing and Analysis, 2010Co-Authors: Joanne Mather, Paul D Rainville, Warren B Potts, Norman W Smith, Robert S PlumbAbstract:A rapid, specific, assay was developed for the benzodiapine alprazolam in rat plasma using sub-2 µm particle liquid chromatography (LC) and tandem quadrupole mass spectrometry (MS/MS). The Limit of Quantification using protein precipitation was determined to 10 pg/mL, whereas the Limit of Quantification using solid-phase extraction (SPE) was determined to be 1.0 pg/mL. The assay was optimized for throughput and resolution of the analyte of interest from the hydroxy metabolite. During the method development process the plasma matrix signal was monitored, for lipids and other endogenous metabolites, to maximize signal response and minimize ion suppression. This was achieved by using a tandem quadrupole mass spectrometer equipped with a novel collision cell design which allowed for the simultaneous collection of full scan MS and multiple reaction monitoring (MRM) data. The lipid profile from the SPE process was significantly less than obtained with the protein precipitation approach. Copyright © 2010 John Wiley & Sons, Ltd.