Luliconazole: Stability-indicating LC method, structural elucidation of major degradation product by HRMS and in silico studies

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,...

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Bibliographic Details
Published in:Revista colombiana de ciencias químico-farmacéuticas 2021, Vol.50 (1)
Main Authors: Porto, Douglas dos Santos, Bajerski, Lisiane, Malesuik, Marcelo Donadel, Braun Azeredo, Juliano, Paula, Fávero Reisdorfer, Soldateli Paim, Clésio
Format: Article
Language:English
Subjects:
Acetonitrile
Antifungal agents
Chromatography
Degradation
Design of experiments
Evaluation
Linearity
Liquid chromatography
Robustness
Selectivity
Stability analysis
Structural stability
Toxicity
Triethylamine
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Summary: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.
ISSN:0034-7418
1909-6356
DOI:10.15446/rcciquifa.v50n1.89717