The Experts below are selected from a list of 354 Experts worldwide ranked by ideXlab platform

Susanne Nussbaumer - One of the best experts on this subject based on the ideXlab platform.

  • Evaluation of chemical contamination of surfaces during the preparation of chemotherapies in 24 hospital pharmacies
    European Journal of Hospital Pharmacy, 2015
    Co-Authors: Sandrine Fleury-souverain, Susanne Nussbaumer, Farshid Sadeghipour, Serge Rudaz, M. Mattiuzzo, Florence Mehl, Lucie Bouchoud, Ludivine Falaschi, Marianne Gex-fabry, Pascal Bonnabry
    Abstract:

    Purpose To evaluate the chemical contamination of surfaces by cytotoxic agents during preparation of injectable chemotherapies in hospital pharmacies. Methods 526 wipe samples collected in 24 Swiss hospital pharmacies were analysed using a validated liquid chromatography–mass spectrometry/mass spectrometry method able to quantify 10 cytotoxic agents: cytarabine, gemcitabine, cyclophosphamide, ifosfamide, methotrexate, Etoposide Phosphate, irinotecan, doxorubicin, epirubicin and vincristine. Information on chemotherapies produced, equipment and production processes used were collected from all the hospital pharmacies on a voluntary basis in order to investigate their association with contamination rates. Results In two pharmacies, no trace of the 10 cytotoxic agents was detected. Chemical contamination was found in the other 22 hospital pharmacies, with combined total contamination of the 10 cytotoxic agents ranging from 8 ng to more than 41 000 ng per sample. Most contaminated samples came from inside biosafety cabinets, but some came from other clean room areas and logistics rooms. Statistically significant associations were observed between contamination rates and sampling locations, the number of chemotherapies prepared per year and types of cleaning solutions used. Conclusions This study demonstrated that most of the hospital pharmacies tested had some contamination of surfaces by different cytotoxic agents. Even if highest levels of contamination were mainly detected inside biosafety cabinets, technicians were also exposed to cytotoxic agents detected in logistical and storage areas. Protective measures should therefore be maintained or even reinforced in these areas in order to limit technicians’ risks of exposure when handling cytotoxic products.

  • wipe sampling procedure coupled to lc ms ms analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces
    Analytical and Bioanalytical Chemistry, 2012
    Co-Authors: Susanne Nussbaumer, Farshid Sadeghipour, Laurent Geiser, Pascal Bonnabry, Denis F Hochstrasser, Jean-luc Veuthey, Sandrine Fleurysouverain
    Abstract:

    A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC–MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm−2) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Pascal Bonnabry - One of the best experts on this subject based on the ideXlab platform.

  • wipe sampling procedure optimisation for the determination of 23 antineoplastic drugs used in the hospital pharmacy
    European Journal of Hospital Pharmacy-Science and Practice, 2021
    Co-Authors: Nicolas Guichard, Pascal Bonnabry, Julien Boccard, Serge Rudaz, Sandrine Souverain
    Abstract:

    Purpose Optimise a wipe sampling procedure to evaluate the surface contamination for 23 antineoplastic drugs used in the hospital pharmacy. Methods The influence of various parameters (ie, sampling device, sampling solution, desorption modes) was evaluated using a validated liquid chromatography–mass spectrometry (LC-MS/MS) method able to quantify 23 antineoplastic drugs widely used in the hospital pharmacy: 5-fluorouracil, busulfan, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, Etoposide, Etoposide Phosphate, fludarabine Phosphate, ganciclovir, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, paclitaxel, pemetrexed, raltitrexed, topotecan and vincristine. Best conditions were tested with real samples from a hospital pharmacy chemotherapy compounding unit. Results Polyester swabs (TX714 and TX716) gave satisfactory results for the desorption step for all compounds with mean recoveries of 90% and 95%, respectively. For the wiping step, higher recoveries were obtained using TX716 and isopropanol 75% as wiping solution. As anticipated, most intense contaminations were found close to the chemotherapy production site, on surfaces the most frequently in contact with operators’ hands. Conclusion Wipe sampling method was successfully developed and applied to real samples to determine surface contamination with 23 antineoplastic agents in trace amounts.

  • Efficacy of Two Cleaning Solutions for the Decontamination of 10 Antineoplastic Agents in the Biosafety Cabinets of a Hospital Pharmacy.
    The Annals of occupational hygiene, 2015
    Co-Authors: Marco Anastasi, Pascal Bonnabry, Serge Rudaz, Thomas Queruau Lamerie, Pascal Odou, Sandrine Fleury-souverain
    Abstract:

    Objective: This study aimed to evaluate two cleaning solutions for the chemical decontamination of antineoplastic agents on the surfaces of two biosafety cabinets routinely used for chemotherapy preparation in a hospital pharmacy. Methods: For almost 1 year (49 weeks), two different solutions were used for the weekly cleaning of two biosafety cabinets in a hospital pharmacy’s centralized cytotoxic preparation unit. The solutions evaluated were a commercial solution of isopropyl alcohol (IPA) and water (70:30, vol:vol), and a detergent solution constituted by 10–2M of sodium dodecyl sulfate (SDS) with 20% IPA. Seven areas in each biosafety cabinet were wiped 14 times throughout the year, before and after the weekly cleaning process, according to a validated procedure. Samples were analyzed using a validated method of high-performance liquid chromatography coupled to mass spectrometry. The decontamination efficacy of these two solutions was tested for 10 antineoplastic agents: cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin, epirubicin, and vincristine. Results: Overall decontamination efficacies observed were 82±6% and 49±11% for SDS solution and IPA, respectively. Higher contamination levels were distributed on areas frequently touched by the pharmacy technicians—such as sleeves and airlock handles—than on scale plates, gravimetric control hardware, and work benches. Detected contaminations of cyclophosphamide, ifosfamide, gemcitabine, and cytarabine were higher than those of the others agents. SDS solution was almost 20% more efficient than IPA on eight of the antineoplastic agents. Conclusion: Both cleaning solutions were able to reduce contamination levels in the biosafety cabinets. The efficacy of the solution containing an anionic detergent agent (SDS) was shown to be generally higher than that of IPA and, after the SDS cleaning procedure, biosafety cabinets demonstrated acceptable contamination levels.

  • Evaluation of chemical contamination of surfaces during the preparation of chemotherapies in 24 hospital pharmacies
    European Journal of Hospital Pharmacy, 2015
    Co-Authors: Sandrine Fleury-souverain, Susanne Nussbaumer, Farshid Sadeghipour, Serge Rudaz, M. Mattiuzzo, Florence Mehl, Lucie Bouchoud, Ludivine Falaschi, Marianne Gex-fabry, Pascal Bonnabry
    Abstract:

    Purpose To evaluate the chemical contamination of surfaces by cytotoxic agents during preparation of injectable chemotherapies in hospital pharmacies. Methods 526 wipe samples collected in 24 Swiss hospital pharmacies were analysed using a validated liquid chromatography–mass spectrometry/mass spectrometry method able to quantify 10 cytotoxic agents: cytarabine, gemcitabine, cyclophosphamide, ifosfamide, methotrexate, Etoposide Phosphate, irinotecan, doxorubicin, epirubicin and vincristine. Information on chemotherapies produced, equipment and production processes used were collected from all the hospital pharmacies on a voluntary basis in order to investigate their association with contamination rates. Results In two pharmacies, no trace of the 10 cytotoxic agents was detected. Chemical contamination was found in the other 22 hospital pharmacies, with combined total contamination of the 10 cytotoxic agents ranging from 8 ng to more than 41 000 ng per sample. Most contaminated samples came from inside biosafety cabinets, but some came from other clean room areas and logistics rooms. Statistically significant associations were observed between contamination rates and sampling locations, the number of chemotherapies prepared per year and types of cleaning solutions used. Conclusions This study demonstrated that most of the hospital pharmacies tested had some contamination of surfaces by different cytotoxic agents. Even if highest levels of contamination were mainly detected inside biosafety cabinets, technicians were also exposed to cytotoxic agents detected in logistical and storage areas. Protective measures should therefore be maintained or even reinforced in these areas in order to limit technicians’ risks of exposure when handling cytotoxic products.

  • wipe sampling procedure coupled to lc ms ms analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces
    Analytical and Bioanalytical Chemistry, 2012
    Co-Authors: Susanne Nussbaumer, Farshid Sadeghipour, Laurent Geiser, Pascal Bonnabry, Denis F Hochstrasser, Jean-luc Veuthey, Sandrine Fleurysouverain
    Abstract:

    A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC–MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm−2) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Sandrine Fleurysouverain - One of the best experts on this subject based on the ideXlab platform.

  • wipe sampling procedure coupled to lc ms ms analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces
    Analytical and Bioanalytical Chemistry, 2012
    Co-Authors: Susanne Nussbaumer, Farshid Sadeghipour, Laurent Geiser, Pascal Bonnabry, Denis F Hochstrasser, Jean-luc Veuthey, Sandrine Fleurysouverain
    Abstract:

    A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC–MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm−2) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Kuo Hsiung Lee - One of the best experts on this subject based on the ideXlab platform.

  • recent progress on c 4 modified podophyllotoxin analogs as potent antitumor agents
    Medicinal Research Reviews, 2015
    Co-Authors: Ying Qian Liu, Jing Tian, Keduo Qian, Xiao Bo Zhao, Susan L Morrisnatschke, Liu Yang, Xiang Nan, Xuan Tian, Kuo Hsiung Lee
    Abstract:

    Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory effect on tumor cell growth led to the development of three of the most highly prescribed anticancer drugs in the world, Etoposide, teniposide, and the water-soluble prodrug Etoposide Phosphate. Their clinical success as well as intriguing mechanism of action stimulated great interest in further modification of PPT for better antitumor activity. The C-4 position has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug resistance. Accordingly, numerous PPT derivatives have been prepared via hemisynthesis and important structure-activity relationship (SAR) correlations have been identified. Several resulting compounds, including GL-331, TOP-53, and NK611, reached clinical trials. Some excellent reviews on the distribution, sources, applications, synthesis, and SAR of PPT have been published. This review focuses on a second generation of new Etoposide-related drugs and provides detailed coverage of the current status and recent development of C-4-modified PPT analogs as anticancer clinical trial candidates.

Fleury-souverain Sandrine - One of the best experts on this subject based on the ideXlab platform.

  • Determination of 16 antineoplastic drugs by capillary electrophoresis with UV detection: Applications in quality control
    'Wiley', 2018
    Co-Authors: Guichard Nicolas, Ogereau Marie, Falaschi Ludivine, Rudaz Serge, Schappler Julie, Bonnabry Pascal, Fleury-souverain Sandrine
    Abstract:

    Two capillary electrophoresis (CE) methods were developed for the analysis of 16 antineoplastic drugs contained in injectable pharmaceutical formulations. A capillary zone electrophoresis (CZE) method coupled to UV was developed with a background electrolyte (BGE) made of a 100 mM Phosphate buffer at pH 2.5 containing 50% (v/v) of acetonitrile and dynamic coating of capillaries with Ceofix®. This method allowed the analysis of doxorubicin, epirubicin, idarubicin, daunorubicin, irinotecan, topotecan, vincristine, vindesine, vinblastine, and vinorelbine in less than 8 min. A micellar electrokinetic chromatography (MEKC) method coupled to UV was also developed for the determination of methotrexate, pemetrexed, Etoposide, Etoposide Phosphate, fludarabine Phosphate and 5-fluorouracil. A run time of 16 min was obtained with a BGE made of 50 mM borate buffer at pH 9.2 with 80 mM of sodium dodecyl sulfate (SDS) and 20% (v/v) of acetonitrile. For both methods, the applied voltage was 30 kV and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in fused silica capillaries with an internal diameter of 50 µm and a total length of 64.5 cm. Both methods were validated and trueness values between 99.4% and 101.3% were obtained with repeatability and intermediate precision values of 0.5-1.8% for all drugs. These methods were found appropriate for controlling injectable pharmaceutical formulations containing antineoplastic drugs and successfully applied in quality control

  • Simultaneous quantification of ten cytotoxic drugs by a validated LC-ESI-MS/MS method
    2018
    Co-Authors: Nussbaumer Susanne, Bonnabry Pascal, Fleury-souverain Sandrine, Antinori Paola, Sadeghipour Farshid, Hochstrasser Denis, Veuthey Jean-luc, Geiser Laurent
    Abstract:

    A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2ngmL−1 for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces. Figure Preparation of cytotoxic formulations at the Pharmacy of Geneva University Hospital

  • Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces
    2018
    Co-Authors: Nussbaumer Susanne, Bonnabry Pascal, Sadeghipour Farshid, Hochstrasser Denis, Veuthey Jean-luc, Geiser Laurent, Fleury-souverain Sandrine
    Abstract:

    A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10ng per wiping sample (i.e. 0.1ngcm−2) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy. Figure Wipe sampling procedure for the determination of cytotoxic drug

  • Evaluation of Decontamination Efficacy of Cleaning Solutions on Stainless Steel and Glass Surfaces Contaminated by 10 Antineoplastic Agents
    2017
    Co-Authors: Queruau Lamerie Thomas, Bonnabry Pascal, Fleury-souverain Sandrine, Nussbaumer Susanne, Décaudin Bertrand, Goossens Jean-françois, Odou Pascal
    Abstract:

    Objectives: The handling of antineoplastic agents results in chronic surface contamination that must be minimized and eliminated. This study was designed to assess the potential of several chemical solutions to decontaminate two types of work surfaces that were intentionally contaminated with antineoplastic drugs. Methods: A range of solutions with variable physicochemical properties such as their hydrophilic/hydrophobic balance, oxidizing power, desorption, and solubilization were tested: ultrapure water, isopropyl alcohol, acetone, sodium hypochlorite, and surfactants such as dishwashing liquid (DWL), sodium dodecyl sulfate (SDS), Tween 40, and Span 80. These solutions were tested on 10 antineoplastic drugs: cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin, epirubicin, and vincristine. To simulate contaminated surfaces, these molecules (200ng) were deliberately spread onto two types of work surfaces: stainless steel and glass. Recovered by wiping with a specific aqueous solvent (acetonitrile/HCOOH; 20/0.1%) and an absorbent wipe (Whatman 903®), the residual contamination was quantified using high-performance liquid chromatography (HPLC) coupled to mass spectrometry. To compare all tested cleaning solutions, a performance value of effectiveness was determined from contamination residues of the 10 drugs. Results: Sodium hypochlorite showed the highest overall effectiveness with 98% contamination removed. Ultrapure water, isopropyl alcohol/water, and acetone were less effective with effectiveness values of 76.8, 80.7, and 40.4%, respectively. Ultrapure water was effective on most hydrophilic molecules (97.1% for cytarabine), while on the other hand, isopropyl alcohol/water (70/30, vol/vol) was effective on the least hydrophilic ones (85.2% for doxorubicin and 87.8% for epirubicin). Acetone had little effect, whatever the type of molecule. Among products containing surfactants, DWL was found effective (91.5%), but its formulation was unknown. Formulations with single surfactant non-ionics (tween 40 and span 80) or anionic (SDS) were also tested. Finally, solutions containing 10-2 M anionic surfactants and 20% isopropyl alcohol had the highest global effectiveness at around 90%. More precisely, their efficacy was the highest (94.8%) for the most hydrophilic compounds such as cytarabine and around 80.0% for anthracyclines. Finally, the addition of isopropyl alcohol to surfactant solutions enhanced their decontamination efficiency on the least hydrophilic molecules. Measured values from the stainless steel surface were similar to those from the glass one. Conclusion: This study demonstrates that all decontamination agents reduce antineoplastic contamination on work surfaces, but none removes it totally. Although very effective, sodium hypochlorite cannot be used routinely on stainless steel surfaces. Solutions containing anionic surfactant such as SDS, with a high efficiency/safety ratio, proved most promising in terms of surface decontaminatio

  • Simultaneous quantification of ten cytotoxic drugs by a validated LC-ESI-MS/MS method
    'Springer Science and Business Media LLC', 2010
    Co-Authors: Nussbaumer Susanne, Bonnabry Pascal, Fleury-souverain Sandrine, Antinori Paola, Sadeghipour Farshid, Hochstrasser Denis, Veuthey Jean-luc, Geiser Laurent
    Abstract:

    A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, Etoposide Phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21 min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2 ng mL(-1) for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces