Identification and characterization of degradation products of indacaterol using liquid chromatography/mass spectrometry

Indacaterol (IND), 5-[2-[(5,6-Diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxyquinolin-2(1H)-one, is an active pharmaceutical ingredient (API) which is used to treat chronic obstructive pulmonary disease (COPD). We followed the International Council for Harmonization (ICH) guide lines to study the degradation behavior of IND under various stress conditions. Stressed degradation of the drug was performed under hydrolytic (alkaline, acidic and neutral), photolytic, oxidative and thermal conditions. Identification and characterization of IND and its forced degradation products (DPs) were demonstrated by using LC-HRMS and MS/MS method. A total of three DPs (DP1-DP3) were identified and characterized. The IND was found to be stable under photolytic, oxidative and thermal conditions, whereas it produced three DPs in acidic, basic and neutral hydrolytic stress conditions.

Download Full-text

Development and Validation of a Stability-Indicating Chromatographic Method for the Determination of Indacaterol Maleate with Glycopyrronium Bromide in Mixture

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180608095420 ◽

2019 ◽

Vol 15 (7) ◽

pp. 694-702

Author(s):

Sonia Talaat Hassib ◽

Hanaa Abdelmenem Hashem ◽

Marwa Ahmed Fouad ◽

Nehal Essam Eldin Mohamed

Keyword(s):

Chromatographic Method ◽

Degradation Products ◽

Reversed Phase ◽

Chronic Obstructive ◽

Forced Degradation ◽

Uv Detector ◽

Obstructive Pulmonary Disease ◽

Mortality And Morbidity ◽

Glycopyrronium Bromide

Introduction: (COPD) Chronic Obstructive Pulmonary Disease is a partially reversible and treatable lung disease, characterized by progressive limitation of airflow. It is one of the main causes of mortality and morbidity worldwide. Methods: An easy, precise and selective reversed-phase liquid chromatographic method, with stabilityindicating assay was established and validated for the determination of indacaterol maleate and glycopyrronium bromide in the mixture. In addition, a forced degradation study was performed for indacaterol maleate, comprised of hydrolysis by acid and base, degradation by oxidation and heat, and photo-degradation. Separation and forced degradation were done by isocratic elution using a reversed phase phenyl column and (methanol: phosphate buffer) at ratio (65:35, v/v) with 3.5 pH buffer as an eluent at 1 mL min-1 as a flow rate. Quantitation was accomplished using a UV detector at 210 nm. Results: The method showed good separation of glycopyrronium bromide, indacaterol maleate and its degradation products. Accuracy, linearity, and precision were acceptable over 10-160 µg mL-1 and 10- 80 µg mL-1 concentration range for indacaterol maleate and glycopyrronium bromide, respectively. Conclusion: The proposed method does not require any previously done separation steps, making it applicable for the analysis of the drugs under investigation in their pharmaceutically marketed preparations.

Download Full-text