Acta Pharm. 65 (2015) 159-169

full paper

Original research paper

Determination of ramipril in human plasma and its fragmentation by UPLC-Q-TOF-MS with positive electrospray ionization

PAWEŁ SZPOT and GRZEGORZ BUSZEWICZ

pawel.szpot@umlub.pl

Laboratory of Forensic Toxicology, Medical University of Lublin, 20-090 Lublin, Poland

Accepted February 4, 2015

This report presents the application of ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry with positive electrospray ionization, to determine ramipril in human plasma. First, the proteins in human plasma were precipitated using acetonitrile, then the supernatant was extracted by ethyl acetate at pH 3 and, finally, the extract was analyzed using a UPLC-Q-TOF-MS system. The method was validated and the coefficient of determination (R²) was > 0.999, the lower limit of quantification (LLOQ) was 0.5 ng mL^–1. Precision, recovery and stability were determined for three different concentrations of ramipril. RSD for this method ranged from 3.3 to 8.6 %. The intra-day mean recovery was from 65.3 to 97.3 %. In addition, the fragmentation of ramipril was studied. Due to high resolution of the spectrometer, it was possible to measure fragment masses accurately and determine their molecular and chemical formulas with high accuracy.

Keywords: ramipril, UPLC-Q-TOF-MS, fragmentation pathway