Delapril and Manidipine Main Degradation Products: LC-UV and LC-ESI-MS Evaluations, Decay Kinetic, and in vitro Cytotoxicity Studies

Abstract

A simple, stability-indicating, and compatible method by liquid chromatography with ultraviolet (LC-UV) and mass spectrometry (LC-MS) detections was developed for the evaluation of delapril (DEL) and manidipine (MAN) degradation products formed under alkaline and photolytic forced conditions, respectively. The chromatographic separation of all compounds was obtained within 7 min and carried out on a C₁₈ column with mobile-phase composed by ammonium acetate and acetonitrile for both techniques. Thereby, the main degradation products detected were studied by LC coupled to electrospray ionization mass spectrometry (LC-ESI-MS). Based on retention times and molecular weight confirmation, a comprehensive degradation pathway for both drugs and the identity of its major products formed could be suggested, without complicated isolation or purification processes. The degradation kinetics of the drugs was also evaluated and could be best described as first-order process for DEL (R² = 0.9991) and zero-order process for MAN (R² = 0.9867). Furthermore, no evidence of cytotoxicity in human mononuclear cells was observed for DEL and MAN degraded samples. The proposed LC-UV method was successfully validated according ICH guidelines and thus helping to improve the quality control of pharmaceuticals.

Keywords:

• cytotoxicity
• degradation kinetics
• delapril
• LC-ESI-MS
• LC-UV
• manidipine

Acknowledgments

The authors confirm that there are no potential sources of conflicts of interest, financial or otherwise.