Development of a stability-indicating UPLC method for terconazole and characterization of the acidic and oxidative degradation products by UPLC-Q-TOF/MS/MS and NMR

Abstract

Terconazole, a triazole antifungal drug, is used to treat infections in the form of a cream or suppositories. A simple, rapid, precise and accurate ultra high performance liquid chromatography method has been developed for the quantitative determination of the terconazole drug substance in the presence of process impurities and degradation products. The method showed adequate separation of terconazole, process impurities and degradation products on a CSH C₁₈ (100 × 2.1 mm, 1.7 μm) column. The mobile phase used was ammonium acetate (10 mM; pH 7.5) and acetonitrile was used as an organic modifier. Terconazole was subjected to forced degradation studies and found to be degraded in acid hydrolytic and oxidative conditions, whereas it was stable under basic, neutral, photolytic and thermal conditions. LC/electrospray ionization and/or LC/atmospheric pressure chemical ionization coupled with quadrupole time-of-flight mass spectrometry have been utilized for identification and structural characterization of the degradation products. The major oxidative degradation products were isolated by preparative HPLC and their structures were confirmed using ¹H NMR and ¹³C NMR. The probable mechanistic explanation is given for the formation of the degradation products. The method was validated in terms of specificity, linearity, accuracy, precision and robustness as per the International Conference on Harmonisation guidelines.