Development, validation and comparison of UHPSFC and UHPLC methods for the determination of agomelatine and its impurities

作者：Plachka Katerina; Chrenkova Lucia; Dousa Michal; Novakova Lucie^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2016, 125: 376-384.

DOI：10.1016/j.jpba.2016.04.020

• Agomelatine
• UHPSFC
• Ultra-high performance supercritical fluid chromatography
• UHPLC
• Ultra-high performance liquid chromatography
• Method development

Agomelatine is one of the newest antidepressants. Due to a different mechanism of action it offers a completely new approach in the treatment of depressive disorders. Two chromatographic methods for determination of agomelatine and its impurities were developed. The separations on UHPSFC system were accomplished using stationary phase based on BEH 2-EP and gradient elution with CO2 and methanol containing 20 mM ammonium formate and 5% of water. The UHPLC separations were performed on stationary phase BEH Shield RP18. The mixture of acetonitrile and methanol in ratio 1:1 and ammonium acetate buffer pH 9.5 were used as mobile phase.
Both developed methods were properly validated in terms of linearity, sensitivity (LOD, LOQ), accuracy and precision according to ICH guidelines. The UHPSFC method was linear in the range 0.25-70 p.g/ml for all analytes with method accuracy >= 97.4% and >= 100.2% and method intra-day precision RSD <= 2.4 and <= 0.8 for impurities and API (active pharmaceutical ingredient), respectively. The UHPLC method was linear in the range 0.1-10 mu g/ml for all analytes except three impurities for which the linear range was larger 0.1-25 mu g/ml. Method accuracy >= 95.7% and >= 95.2% and method intra-day precision RSD <= 2.6 and <= 1.5 were found for impurities and API, respectively.
The measurement of tablet samples was performed and the selected parameters of the methods were compared. In conclusion, both methods were appropriate for the determination of agomelatine and its impurities in pharmaceutical quality control (QC), although the UHPSFC method was found as more convenient especially in the method development phase. The advantages of newly developed UHPSFCPDA (photo diode array detector) method were its environmental friendliness due to the mobile phase used, a very good resolution, selectivity and high speed of analysis (total time of separation was 4.1 min).

• 出版日期2016-6-5