Determination of Genotoxic Azide Impurity in Cilostazol API by Ion Chromatography with Matrix Elimination

Abstract

Cilostazol is a commonly used active pharmaceutical ingredient (API) to treat and reduce the symptoms of intermittent claudication in peripheral vascular disease. Recently, it was found to be a potential medicine in the effective treatment of COVID-19. In addition to the positive effects of this API, genotoxic sodium azide is used in the synthesis of cilostazol that can appear in the API. In this work, a method was developed for the determination of sodium azide (as azide anion) in cilostazol API at 7.5 ppm limit level by using ion chromatography (IC) and liquid–liquid extraction (LLE) sample preparation. The liquid–liquid extraction allows the application of high sample concentrations. Because of the low limit concentration (7.5 ppm), 500 mg sample was dissolved in 5 mL solvent. By using LLE for sample preparation, the huge amount of cilostazol was omitted and column overload was avoided. The developed method was validated in accordance with the relevant guidelines. Specificity, accuracy, precision, limit of detection and limit of quantification parameters were evaluated. The calculated limit of detection was 0.52 ppm (S/N:3) and the limit of quantification was 1.73 ppm (S/N:10) for sodium azide. The recovery of the sodium azide was 102.4% and the prepared solutions were stable in the sample holder for 24 h.

Keywords

• azide
• cilostazol
• COVID-19
• genotoxic impurity
• validation
• LLE