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A validated LC-MS/MS assay for the quantification of phosphodiesterase-5 inhibitors in human plasma.
de Souza Madeira, Camilla Regina; Millan Fachi, Mariana; Concentino, Victor; de Fátima Cobre, Alexandre; Leal Badaró Trindade, Angela Cristina; Gonçalves, Alan Guilherme; Pontarolo, Roberto.
Afiliación
  • de Souza Madeira CR; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil.
  • Millan Fachi M; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil.
  • Concentino V; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil.
  • de Fátima Cobre A; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil.
  • Leal Badaró Trindade AC; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil.
  • Gonçalves AG; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil.
  • Pontarolo R; Universidade Federal do Paraná, Department of Pharmacy, 632 Lothário Meissner Avenue, 80210-170 Curitiba, PR, Brazil. Electronic address: pontarolo@ufpr.br.
Article en En | MEDLINE | ID: mdl-34147872
Phosphodiesterase inhibitors (PDE5i) are considered the first line therapy for erectile dysfunction. All PDE5i available on the market are structurally related; their main differences relate to their pharmacokinetic parameters. For these treatments to be effective and safe, it is necessary that these drugs are in the appropriate doses and that they reach adequate concentrations in the plasma. For this purpose, it is essential to perform therapeutic monitoring using bioanalytical methods. In this way, the present work aimed to develop and validate a new bioanalytical method, based on LC-MS/MS, for the simultaneous quantification of six commercially available PDE5i (avanafil, lodenafil, sildenafil, tadalafil, udenafil, and vardenafil). For this purpose, the human plasma was extracted with diethyl ether and sulfaquinoxaline was established as an internal standard. Separation was achieved using an Xbridge C18 column at 40 °C as the stationary phase, using water and acetonitrile as the mobile phase (both with formic acid and ammonium formate) in gradient mode. The method was validated according to the current guidelines and was found to be selective, linear (from 1 to 200 ng.mL-1 for all drugs except for tadalafil which is from 5 to 200 ng.mL-1), precise, accurate, and free of residual and matrix effects. The drugs were considered stable in plasma and in solution under different conditions. The method was applied to volunteerssamples, demonstrating that the method can be used routinely and may be useful in future studies on pharmacokinetics and therapeutic monitoring.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / Espectrometría de Masas en Tándem / Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 Tipo de estudio: Guideline / Prognostic_studies Límite: Adult / Humans / Male Idioma: En Revista: J Chromatogr B Analyt Technol Biomed Life Sci Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / Espectrometría de Masas en Tándem / Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 Tipo de estudio: Guideline / Prognostic_studies Límite: Adult / Humans / Male Idioma: En Revista: J Chromatogr B Analyt Technol Biomed Life Sci Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos