Stability-indicating LC method for the quantification of Midazolam active pharmaceutical ingredient and in pharmaceutical formulations

Daiane Anzilaggo; Bádila Regina Dalla Costa; Luciana Grazziotin Rossato-Grando; Hellen Karine Stulzer; Charise Dallazem Bertol

doi:10.22456/2527-2616.86375

Authors

Daiane Anzilaggo Laboratório de Controle de Qualidade - Curso de Farmácia - Programa de Pós-Graduação em Envelhecimento Humano - Universidade de Passo Fundo
Bádila Regina Dalla Costa Laboratório de Controle de Qualidade - Curso de Farmácia - Programa de Pós-Graduação em Envelhecimento Humano - Universidade de Passo Fundo
Luciana Grazziotin Rossato-Grando Laboratório de Controle de Qualidade - Curso de Farmácia - Programa de Pós-Graduação em Envelhecimento Humano - Universidade de Passo Fundo
Hellen Karine Stulzer Universidade Federal de Santa Catarina
Charise Dallazem Bertol Laboratório de Controle de Qualidade - Curso de Farmácia - Programa de Pós-Graduação em Envelhecimento Humano - Universidade de Passo Fundo

DOI:

https://doi.org/10.22456/2527-2616.86375

Keywords:

Forced degradation, HPLC, Injections, Quality control, Stress test, Tablets

Abstract

A stability-indicating LC method was validated for the quantification of midazolam (MDZ) active pharmaceutical ingredient (API) and in pharmaceutical formulations. Isocratic chromatography was performed on C₁₈ column with mobile phase containing methanol/acetonitrile/water (45:35:20 v/v/v) with 0.4% of triethylamine pH 6.5. The validation included specificity, linearity, accuracy, precision and robustness. In specificity, after acid, basic, neutral, oxidant and thermal degradation, it was found that the concentration of MDZ decreased substantially, with the appearance of peaks representatives of the degradation products, proving the stability-indicating power of the method. The response was linear in the range 50.0 – 250.0 µg.mL^-1, with 11.73 µg.mL^-1 and 3.87 µg.mL^-1as LOQ and LOD, respectively. Recoveries ranged between 98.68 and 100.41%. The relative standard deviation values for intra and interday precision were 1.11%, 0.82% and 1.47%, respectively. The tablets and injections containing MDZ were approved in the assay and content uniformity. The method can be adopted by pharmacopeias and for routine quality control for analysis of MDZ API, tablets and injection.

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