RESUMEN
The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We validated this method following Mexican and international guidelines. ARV drugs. We extracted the ARV drugs from 200 µL samples of breast milk and detected these drugs in a triple quadrupole mass spectrometer with positive electrospray ionization. The validated concentration ranges (ng/mL) for zidovudine, lamivudine, lopinavir, and ritonavir were 12.5-750, 50-2500, 100-5000 and 5 to 250, respectively. Additionally, the absolute recovery percentages (and matrix effects) were 91.4 (8.39), 88.78 (28.75), 91.38 (11.77) and 89.78 (12.37), respectively. We determined that ARV drugs are stable for 24 h at 8°C and 24°C for 15 days at -80°C. This methodology had the capacity for simultaneous detection; separation; and accurate, precise quantification of ARV drugs in human breast milk samples according to Mexican standard laws and United States Food and Drug Administration guidelines.
Asunto(s)
Fármacos Anti-VIH/análisis , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Leche Humana/química , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/normas , Lactancia Materna , Calibración , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida de Alta Presión/normas , Calostro/química , Femenino , Infecciones por VIH/prevención & control , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/análisis , Lopinavir/análisis , Embarazo , Complicaciones Infecciosas del Embarazo/metabolismo , Estándares de Referencia , Reproducibilidad de los Resultados , Ritonavir/análisis , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masas en Tándem/normas , Adulto Joven , Zidovudina/análisisRESUMEN
A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N(6)-(ferrocenmethyl)quinazolin-2,4,6-triamine (H2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electrochemical studies showed the importance of both the ferrocene and the heterocyclic nucleus to the observed activity. H2 is readily oxidized electrochemically, indicating that the mechanism of action probably involves redox reactions.