Analysis of eflucimibe and related impurities by highly sensitive liquid chromatography‐electrospray‐tandem mass spectrometry

Abstract Eflucimibe (F 12511) is a new and promising acyl‐coenzyme A cholesterol O‐acyl‐transferase (ACAT) inhibitor, developed at the Pierre Fabre Research Center for the treatment of atherosclerosis. Owing to the synthetic pathway, residual impurities may be present (at very low levels) in the final product, which is currently analysed by high‐performance liquid chromatography (HPLC) with UV detection. In this work, a faster, specific, and sensitive analytical method has been developed for the determination of eflucimibe and its four related impurities. Electrospray‐tandem mass spectrometry (ESI‐MS/MS) coupled with HPLC is demonstrated to efficiently enhance the detection limits (at least 1200‐fold), within a 4‐minute run time. After optimisation of the ESI and MS/MS parameters for each of the five compounds, quantitative analysis was performed in the multiple reaction monitoring (MRM) mode and the calibration curves yielded correlation coefficients (r ) greater than 0.9996. Finally, this method was successfully applied to the assay of a real batch sample.