Fragmentation study of simvastatin and lovastatin using electrospray ionization tandem mass spectrometry.
The fragmentation mechanism of simvastatin and lovastatin was investigated using both triple quadrupole and ion trap mass spectrometers. The elimination of the ester side-chain followed by dehydration and dissociation of the lactone moiety were observed as the main fragmentation pathways for both compounds. Another major fragmentation process was a C==C double-bond facilitated rearrangement. Our tandem mass spectrometric (MS/MS) data suggested that the beta-hydroxy group was involved in the fragmentation by interacting with the carboxyl group generated from the ring opening of the lactone. As a result, a facile neutral loss of 60 Da (CH(3)COOH or a combination of CH(2)==C==O and H(2)O) was detected. MS/MS studies of the structural analogs also provided evidence that the dehydration of the beta-hydroxy lactone generated preferentially the beta,gamma-unsaturated lactones.
Wang
H
H
Pharmaceutical Research and Development, Merck Research Laboratories, P.O. Box 4, WP78-302, West Point, Pennsylvania 19486, USA. hongmike_wang@merck.com
Wu
Y
Y
Zhao
Z
Z
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry*; D008148:Lovastatin / Q000737:chemistry*; D015394:Molecular Structure; D019821:Simvastatin / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019821:Simvastatin