Lisinopril Compounds Mass Spectrometry

Since the introduction of electrospray ionization(ESI),mass spectrometry(MS) has played an important role in biomolecular and drug analyses because it is highly sensitive,while tandem mass spectrometry(MS/MS)provides structure information. Herein,using this technique,we have performed the following procedures on lisinopril,its RSS diastereomer,and impurities in bulk drug lisinopril:1.Lisinopril,its RSS isomer,and their derivatives were differentiated by both protonated and lithium added ions.First,we differentiated the two pairs of diastereomers using the CID spectra of the protonated ions.The ion at m/z 246 was more abundant than the ion at m/z 245 for lisinopril.In contrast,the former had less abundant RSS isomer than the latter.Therefore,it was shown that lisinopril was distinguished from its RSS isomer by the CID of the protonated ions.Similar differences have been likewise observed among the CID mass spectra of their derivatives.We also differentiated the two pairs of diastereomers using the CID spectra of their lithium adducted ions.For lisinopril,the ion at m/z 297 was about three times higher than that of the ions at m/z 315;the former was nearly the same as that of the latter for RSS isomer.A significant difference was found in the CID spectra of the lithium adducted ions between these two diastereomers,thereby providing the clue for chiral recognition.Similar differences were also observed between the CID mass spectra of their derivatives.2.A rapid,sensitive,and practical method for the structural elucidation of the trace impurities in bulk drug lisinopril by HPLC-MS~n and FTICR-MS analysis has been developed.Using this method,the fragmentation behavior of lisinopril was investigated,and two unknown impurities were rapidly identified and further confirmed by NMR experiments after preparative isolation.In addition,the differentiation of isomers by mass spectrometry and the application of LC-MS in drug development were also reviewed.