Development and Validation of Different Chromatographic Methods for Analysis of Cabergoline in the Presence of Its Degradation Products: Studying Degradation Profile

Abstract

Cabergoline is widely used as a prolactin secretion inhibitor and as a treatment for Parkinson’s disease. Studying the structure of cabergoline, it contains a urea moiety and an amide group which are sensitive to degradation by hydrolysis as well as an alkene bond that is susceptible to oxidation. Degradation was performed regarding ICH recommendations including hydrolysis (pH from 1.3 to 12.7 using HCl or NaOH with different molarities), oxidation, photo, and thermal degradations. The drug was highly sensitive to all studied conditions except thermal degradation with the production of three major degradation products which were isolated and identified using IR and MS analyses. Two stability indicating chromatographic methods were developed for quantification of the drug in the presence of its degradation products. The first method was HPTLC which depended on using a developing system of butanol:methanol:triethyl amine (95:5:10, by volume) and UV scanning at 280 nm. The second method was HPLC at which the drug and degradation products were separated within 5 min using acetonitrile: 0.05% aqueous triethylamine (TEA) (pH adjusted to 6.5 using 1% aqueous H3PO4) [70:30, v/v] and UV scanning was performed at 225 nm. Validation parameters were calculated according to ICH recommendations and all parameters were within the acceptable limits. Comparison was made between the developed methods and the previously published ones; the developed methods were found to be superior regarding analysis time, studying different degradation pathways, and identifying the degradation products.