J. Pharm. Pharmacogn. Res., vol. 10, no. 5, pp. 847-856, September-October 2022.

DOI: https://doi.org/10.56499/jppres22.1433_10.5.847

Original Article

Development and validation of ultraviolet spectrophotometric methods for lamivudine and zidovudine quantification in dissolution test

[Desarrollo y validación de métodos espectrofotométricos ultravioleta para la cuantificación de lamivudina y zidovudina en pruebas de disolución]

Enma Perez-Chauca^1*, Pedro M. Alva-Plasencia², Humberto Gomes Ferraz³

¹Unidad de Posgrado en Farmacia y Bioquímica, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo, 13011, Perú.

²Departamento de Farmacotecnia, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo, 13011, Perú.

³Faculdade de Ciências Farmacêuticas, Universidad de São Paulo, Av. Prof. Lineu Prestes 580-Cidade universitária, 05508-900, São Paulo, Brasil.  

*E-mail: eperez@unitru.edu.pe

Abstract

Context: In the development of a good analytical method, the selection of appropriate conditions for quantifying drugs is essential. The method validation should be determined before conducting the dissolution test.

Aims: To develop and validate two analytical methods by UV spectrophotometry to quantify lamivudine and zidovudine in dissolution test.

Methods: The dissolution conditions were 900 mL of dissolution medium (pH 1.2, pH 4.5, and pH 6.8), using paddles, at 75 rpm, and sampling time points of 5, 10, 15, 20, and 30 minutes. The analytical methods were developed by scanning analytical solutions in the UV region. The proposed methods were validated in accordance with the ICH guideline and the United States Pharmacopoeia.

Results: Lamivudine showed wavelengths at 280 nm, 273 nm, and 270 nm in buffers at pH 1.2, pH 4.5, and pH 6.8, respectively; while zidovudine showed a wavelength at 266 nm in all three buffers. Regression analysis confirmed linearity (r2>0.998). Placebos and diluents showed no analytical interference. LOD and LOQ were lower than the linearity range. Recovery percentages were within 95% to 105%. RSD values were below 2% and 7% for repeatability and intermediate precision, respectively. No changes introduced modified the method response. The analytical solutions were stable until 24 hours. The results showed that Whatman No 41, No 42, and PVDF 0.45 µm filters can be used.

Conclusions: The proposed analytical methods demonstrated linearity, specificity, accuracy, and precision. In addition, LOD and LOQ, robustness, stability of the analytical solution, and filter test showed satisfactory results.

Keywords: analytical methods; drug dissolution; reverse transcriptase inhibitors; spectrophotometry.

Resumen

Contexto: En el desarrollo de un buen método analítico, la selección de las condiciones adecuadas para cuantificar los fármacos es esencial. La validación del método debe determinarse antes de realizar las pruebas de disolución.

Objetivos: Desarrollar y validar dos métodos analíticos por espectrofotometría UV para cuantificar lamivudina y zidovudina en pruebas de disolución.

Métodos: Las condiciones de disolución fueron de 900 mL de medio de disolución (pH 1,2; pH 4,5 y pH 6,8), utilizando paletas, a 75 rpm, y puntos de tiempo de muestreo de 5, 10, 15, 20 y 30 minutos. Los métodos analíticos se desarrollaron mediante el escaneo de las soluciones analíticas en la región UV. Los métodos propuestos fueron validados de acuerdo con la directriz ICH y la Farmacopea de los Estados Unidos.

Resultados: Lamivudina mostró longitudes de onda a 280 nm, 273 nm y 270 nm en tampones a pH 1,2; pH 4,5 y pH 6,8, respectivamente; mientras que zidovudina mostró una longitud de onda de 266 nm en los tres tampones. El análisis de regresión confirmó la linealidad (r2>0,998). Los placebos y diluyentes no mostraron interferencia analítica. El LOD y LOQ fueron más bajos que el rango de linealidad. Los porcentajes de recuperación estuvieron dentro del 95% al 105%. Los valores de RSD fueron inferiores al 2% y 7% para la repetibilidad y la precisión intermedia, respectivamente. Ningún cambio introducido modificó la respuesta del método. Las soluciones analíticas fueron estables hasta las 24 horas. Los resultados mostraron que se pueden utilizar filtros Whatman No 41, No 42 y PVDF 0,45 μm.

Conclusiones: Los métodos analíticos propuestos demostraron linealidad, especificidad, exactitud y precisión. Además, LD y LC, la robustez, la estabilidad de la solución analítica y la prueba de filtro mostraron resultados satisfactorios.

Palabras Clave: métodos analíticos; disolución de fármacos; inhibidores de la transcriptasa inversa; espectrofotometría.

Citation Format: Perez-Chauca E, Alva-Plasencia PM, Ferraz HG (2022) Development and validation of ultraviolet spectrophotometric methods for lamivudine and zidovudine quantification in dissolution test. J Pharm Pharmacogn Res 10(5): 847–856. https://doi.org/10.56499/jppres22.1433_10.5.847

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