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Antonio Davolio – One of the best experts on this subject based on the ideXlab platform.

  • uplc ms ms method for the simultaneous quantification of three new Antiretroviral Drugs dolutegravir elvitegravir and rilpivirine and other thirteen Antiretroviral agents plus cobicistat and ritonavir boosters in human plasma
    Journal of Pharmaceutical and Biomedical Analysis, 2017
    Co-Authors: Marco Simiele, Stefano Bonora, Alessandra Ariaudo, Amedeo De Nicolo, Fabio Favata, Martina Ferrante, Chiara Carcieri, Giovanni Di Perri, Antonio Davolio

    Abstract:

    Abstract Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest Antiretroviral Drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these Drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other Antiretroviral Drugs. In this work, we describe the development and validation of a new UPLC–MS/MS method to quantify these Drugs, together with other fourteen Antiretroviral agents, in human plasma. One hundred microliters of plasma samples were added with internal standard (6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline), underwent a simple protein precipitation with methanol:acetonitrile (50:50 v/v) followed by sample dilution with water. Chromatographic separation was performed on a Acquity® UPLC HSS T3 column (150 mm x 2.1 mm I.D) with a particle size of 1.8 μm and compounds were detected with a tandem mass detector, monitoring two ion transitions for each Drugs. The mean recovery of RPV, DTG and EVG were 101%, 87% and 112.3% respectively. Accuracy and precision inter/intra-day were below 15% for all Drugs, in accordance to Food and Drug Administration guidelines requirements. The UPLC–MS/MS method reported here could be used routinely to monitor plasma concentrations of antiviral Drugs, including RPV, DTG and EVG.

Peter I Pillans – One of the best experts on this subject based on the ideXlab platform.

  • the current role of liquid chromatography tandem mass spectrometry in therapeutic drug monitoring of immunosuppressant and Antiretroviral Drugs
    Clinical Biochemistry, 2011
    Co-Authors: Paul J Taylor, Chunhui Tai, Michael E Franklin, Peter I Pillans

    Abstract:

    Therapeutic drug monitoring of critical dose immunosuppressant Drugs is established clinical practice and there are similar good reasons to monitor Antiretrovirals. The aim of this article is to review the recent literature (last five years), with particular reference to the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS offers many potential advantages. The superior selectivity of LC-MS/MS over immunoassays for immunosuppressant Drugs has been widely reported. Simultaneous measurement of a number of Drugs can be performed. It is currently routine practice for the four major immunosuppressants (cyclosporin, tacrolimus, sirolimus and everolimus) to be simultaneously measured in whole blood. While up to 17 Antiretroviral Drugs have been simultaneously measured in plasma. The exquisite sensitivity of LC-MS/MS also provides the opportunity to measure these Drugs in alternative matrices, such as dried blood spots, saliva, peripheral blood mononuclear cells and tissue. However, the clinical utility of measuring these classes of Drugs in alternative matrices is still to be determined.

Stefano Bonora – One of the best experts on this subject based on the ideXlab platform.

  • A review of the potential mechanisms of neuronal toxicity associated with Antiretroviral Drugs
    Journal of NeuroVirology, 2020
    Co-Authors: Ilaria De Benedetto, Mattia Trunfio, Giulia Guastamacchia, Stefano Bonora, Andrea Calcagno

    Abstract:

    Highly active Antiretroviral treatment has led to unprecedented efficacy and tolerability in people living with HIV. This effect was also observed in the central nervous system with the nowadays uncommon observation of dementias; yet in more recent works milder forms are still reported in 20–30% of optimally treated individuals. The idea of a subclinical neuronal toxicity induced by Antiretrovirals has been proposed and was somehow supported by the late-emerging effects associated with efavirenz use. In this manuscript we are reviewing all the potential mechanisms by which Antiretroviral Drugs have been associated with in vitro, ex vivo, or in vivo toxicity to cells pertaining to the central nervous system (neurons, astrocytes, oligodendrocytes, and endothelial cells). These include direct or indirect effects and pathological pathways such as amyloid deposition, damage to small cerebral vessels, and impairment in neurotransmission. The aim of this review is therefore to provide a detailed description of the available literature in order to guide further clinical research for improving patients’ neurocognition and quality of life.

  • uplc ms ms method for the simultaneous quantification of three new Antiretroviral Drugs dolutegravir elvitegravir and rilpivirine and other thirteen Antiretroviral agents plus cobicistat and ritonavir boosters in human plasma
    Journal of Pharmaceutical and Biomedical Analysis, 2017
    Co-Authors: Marco Simiele, Stefano Bonora, Alessandra Ariaudo, Amedeo De Nicolo, Fabio Favata, Martina Ferrante, Chiara Carcieri, Giovanni Di Perri, Antonio Davolio

    Abstract:

    Abstract Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest Antiretroviral Drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these Drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other Antiretroviral Drugs. In this work, we describe the development and validation of a new UPLC–MS/MS method to quantify these Drugs, together with other fourteen Antiretroviral agents, in human plasma. One hundred microliters of plasma samples were added with internal standard (6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline), underwent a simple protein precipitation with methanol:acetonitrile (50:50 v/v) followed by sample dilution with water. Chromatographic separation was performed on a Acquity® UPLC HSS T3 column (150 mm x 2.1 mm I.D) with a particle size of 1.8 μm and compounds were detected with a tandem mass detector, monitoring two ion transitions for each Drugs. The mean recovery of RPV, DTG and EVG were 101%, 87% and 112.3% respectively. Accuracy and precision inter/intra-day were below 15% for all Drugs, in accordance to Food and Drug Administration guidelines requirements. The UPLC–MS/MS method reported here could be used routinely to monitor plasma concentrations of antiviral Drugs, including RPV, DTG and EVG.