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Luliconazole: Stability-indicating LC method, structural elucidation of major degradation product by HRMS and in silico studies
Luliconazol: método por LC indicativo de estabilidad, elucidación estructural del producto de degradación mayoritario por HRMS y estudios in silico
Luliconazol: método LC indicativo de estabilidade, elucidação estrutural do principal produto de degradação por HRMS e estudos in sílico
DOI:
https://doi.org/10.15446/rcciquifa.v50n1.89717Keywords:
Luliconazole, stability-indicating method, forced degradation, degradation product, in silico study, zeneth software. (en)Luliconazol, método indicativo de estabilidade, degradação forçada, produto de degradação, estudos in silico, software zeneth. (pt)
Luliconazol, método indicativo de la estabilidad, degradación forzada, producto de degradación, estudios in silico, software zeneth. (es)
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Aim: A new stability-indicating liquid chromatography method was developed and validated for the quantitative determination of luliconazole. Materials and methods: Preliminary forced degradation study demonstrated an additional peak of the degradation product at the same retention time to the drug, due to this, the method was developed optimizing the chromatographic conditions to provide sufficient peak resolution (R ≥ 2). The experimental design was evaluated to assess the robustness and the best chromatographic conditions to be used for the validation. Methodology: Luliconazole solutions were exposed to various stress conditions to evaluate the method indication stability, in which the degradation product (DP-1) formed was isolated, identified, and evaluated in silico to predict degradation pathway and toxicity. The procedure was validated by robustness, selectivity, linearity, precision, and accuracy. Liquid chromatography was performed in a Phenomenex® RP-18 column with a mixture of acetonitrile and 0.3% (v/v) triethylamine solution as a mobile phase in isocratic elution. Results and conclusions: The method demonstrated robustness, good recovery, precision, linear response over a range from 5.0 to 40.0 μg.mL-1, and to be stability indicating. The alkaline stress condition resulted in the formation of DP-1. hrms studies identified this product as an hydroxyacetamide derivative, and in silico studies did not show toxic potential.
Objetivo: un nuevo método indicativo de estabilidad por cromatografía líquida fue desarrollado y validado para la determinación cuantitativa de luliconazol. Materiales y métodos: estudios preliminares de degradación forzada demostraron un pico adicional en el mismo tiempo de retención del fármaco. El método desarrollado para optimizar las condiciones cromatográficas proporcionó una adecuada resolución (R ≥ 2). El diseño experimental fue evaluado para verificar su robustez y la mejor condición cromatográfica para validación. Metodología: las soluciones de luliconazol fueron expuestas a diferentes condiciones de estrés para evaluar la indicación de estabilidad del método, el aislamiento del producto de degradación formado (DP-1), su identificación y análisis in silico para predecir su ruta de degradación y toxicidad. El procedimiento se validó por robustez, selectividad, linealidad, precisión y exactitud. Las condiciones cromatográficas incluyeron una columna Phenomenex® RP-18, como fase móvil una mezcla de acetonitrilo y solución 0,3% (v/v) de trietilamina en elución isocrática. Resultados y conclusiones: el método mostró ser robusto, con buena recuperación, precisión, respuesta lineal en el rango de 5,0 a 40,0 μg.mL-1 e indicativo de la estabilidad. La condición de estrés alcalina resultó en la formación de DP-1. Estudios por hrms identificaron este producto como un derivado hidroxiacetamida y los estudios in silico no mostraron potencial de toxicidad.
Objetivo: um novo método indicativo de estabilidade por cromatografia líquida foi desenvolvido e validado para a determinação quantitativa de luliconazol. Materiais e métodos: estudos preliminares de degradação forçada demonstraram um pico adicional no mesmo tempo de retenção do medicamento. O método desenvolvido para otimizar as condições cromatográficas proporcionou resolução adequada (R ≥ 2). O delineamento experimental foi avaliado para verificar sua robustez e a melhor condição cromatográfica para validação. Metodologia: soluções de luliconazol foram expostas a diferentes condições de estresse para avaliar a indicação da estabilidade do método, o isolamento do produto de degradação formado (DP-1), sua identificação e análise in silico para predizer sua rota de degradação e toxicidade. O procedimento foi validado quanto à robustez, seletividade, linearidade, precisão e exatidão. As condições cromatográficas incluíram uma coluna Phenomenex® RP-18, como fase móvel uma mistura de acetonitrila e solução de trietilamina 0,3% (v/v) em eluição isocrática. Resultados e conclusões: o método mostrou-se robusto, com boa recuperação, precisão, resposta linear na faixa de 5,0 a 40,0 μg.mL-1 e indicativo de estabilidade. A condição de estresse alcalino resultou na formação de DP-1. Os estudos da hrms identificaram este produto como um derivado da hidroxiacetamida e os estudos in silico não mostraram nenhum potencial de toxicidade.
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