Development and validation of a stability indicating method for seven novel derivatives of lamivudine with anti-HIV and anti-HBV activity in simulated gastric and intestinal fluids

• Autores: Gualdesi, María Soledad; Esteve Romero, Josep; Briñon, Margarita Cristina; Raviolo, Mónica Ana
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Lamivudine Derivatives; Micellar Liquid Chromatography; Simulated Gastric And Intestinal Fluids; Pharmacokinetics
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

A simple micellar liquid chromatography (MLC) method has been developed and validated for use in stability indicating studies of lamivudine and its carbonate derivatives with proved activity against human immunodeficiency and hepatitis B viruses (HIV and HBV, respectively), in simulated gastric (SGF) and intestinal (SIF) fluids samples. The optimized method involves a C18 column thermostated at 30 °C, UV detection at 272 nm, a flow rate of 1.0 mL min−1 and a micellar mobile phase composed by 0.15 M sodium dodecyl sulphate (SDS) – 4% (v/v) 1-butanol – 0.01 M KH2PO4–Na2HPO4 (pH 7), using zidovudine (AZT) as internal standard. Validation under Food and Drug Administration (FDA) guideline of the analytical parameters include: linearity (r2 > 0.9996), LODs (1.6 × 10−7–6.9 × 10−6 M) and LOQ (1 × 10−5 M), intra (0.02–1.48%) and inter-day precision (0.04–1.66%) expressed as relative standard deviation (R.S.D.), and robustness parameters (less than 1.98%). Using this method, recoveries ranging from 92.9 to 119% were obtained for the eight substances. Thus, this method provides a simple, sensitive, accurate and precise assay for the determination of all compounds that can be readily adaptable to routine use by clinical laboratories with standard equipment. In addition, we evaluated the stability of carbonates of lamivudine in buffer pH 1.2 and 6.8; SGF (pH 1.2) and SIF one (pH 6.8), all as indicated in United States Pharmacopeia (USP) 32. Finally, this chromatographic method was applied to stability studies which resulted in all the compounds following a pseudo-first-order kinetics, and in the determination of its kinetic constant and half-life time.
Fil: Gualdesi, María Soledad. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Esteve Romero, Josep. Universitat Jaume I; España
Fil: Briñon, Margarita Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Raviolo, Mónica Ana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina