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2030-12-31
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- CDTS - Artigos de Periódicos [363]
- INI - Artigos de Periódicos [3393]
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DEVELOPMENT AND VALIDATION OF LC–MS/MS METHODS FOR THE SIMULTANEOUS QUANTIFICATION OF SOFOSBUVIR AND ITS MAJOR METABOLITE (GS-331007) IN BLOOD PLASMA AND CEREBROSPINAL AND SEMINAL FLUID: APPLICATION TO A PILOT CLINICAL TRIAL WITH A FOCUS ON ZIKA
Author
Vilhena, Leandro Schiavo
Silva, Aline Campos de Azevedo da
Silva, Diego Medeiros dias da
Pinto, Douglas Pereira
Coelho, Estephane Fernandes
Araújo, João Felipe Garcia Medeiros de
Silveira, Gabriel Parreiras Estolano da
Pereira, Heliana Martins
Silva, Letícia de Sá Fernandes Vallim da
Marins, Rita de Cássia Elias Estrela
Bortolini, Roberta Ghilosso
Souza, Thiago Moreno L.
Veloso, Valdiléa G.
Nascimento, Viviane de Assis
Amendoeira, Fábio Coelho
Fonseca, Laís Bastos da
Silva, Aline Campos de Azevedo da
Silva, Diego Medeiros dias da
Pinto, Douglas Pereira
Coelho, Estephane Fernandes
Araújo, João Felipe Garcia Medeiros de
Silveira, Gabriel Parreiras Estolano da
Pereira, Heliana Martins
Silva, Letícia de Sá Fernandes Vallim da
Marins, Rita de Cássia Elias Estrela
Bortolini, Roberta Ghilosso
Souza, Thiago Moreno L.
Veloso, Valdiléa G.
Nascimento, Viviane de Assis
Amendoeira, Fábio Coelho
Fonseca, Laís Bastos da
Affilliation
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Laboratório de Pesquisa Clínica em DST e AIDS. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Faculty of Pharmacy. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Cidade Universitária. Rio de Janeiro, RJ, Brasil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. STD and AIDS Clinical Research Laboratory - Management. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. National Institute for Quality Assurance in Health. Department of Pharmacodynamics and Physiology. Pharmacology Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Laboratório de Pesquisa Clínica em DST e AIDS. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Faculty of Pharmacy. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Cidade Universitária. Rio de Janeiro, RJ, Brasil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. STD and AIDS Clinical Research Laboratory - Management. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. National Institute for Quality Assurance in Health. Department of Pharmacodynamics and Physiology. Pharmacology Laboratory. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Health Technology Development Center. Equivalence and Pharmacokinetics Laboratory. Rio de Janeiro, RJ, Brazil.
Abstract
Zika still poses a threat to global health owing to its association with serious neurological conditions and the absence of a vaccine and treatment. Sofosbuvir, an anti-hepatitis C drug, has shown anti-Zika effects in animal and cell models. Thus, this study aimed to develop and validate novel LC-MS/MS methods for the quantification of sofosbuvir and its major metabolite (GS-331007) in human plasma and cerebrospinal (CSF) and seminal fluid (SF), and apply the methods to a pilot clinical trial. The samples were prepared by liquid-liquid extraction and separated using isocratic mode on Gemini C18 columns. Analytical detection was performed using a triple quadrupole mass spectrometer equipped with an electrospray ionization source. The validated ranges for sofosbuvir were 0.5-2,000 ng/mL (plasma) and 0.5-100 ng/mL (CSF and SF), while for the metabolite they were 2.0-2,000 ng/mL (plasma), 5.0-200 ng/mL (CSF) and 10-1,500 ng/mL (SF). The intra-day and inter-day accuracies (90.8-113.8%) and precisions (1.4-14.8%) were within the acceptance range. The developed methods fulfilled all validation parameters concerning selectivity, matrix effect, carryover, linearity, dilution integrity, precision, accuracy and stability, confirming the suitability of the method for the analysis of clinical samples.
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