title: Fragmentation study of simvastatin and lovastatin using electrospray ionization tandem mass spectrometry.
abstract: 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.
authors.affiliation: Pharmaceutical Research and Development, Merck Research Laboratories, P.O. Box 4, WP78-302, West Point, Pennsylvania 19486, USA. hongmike_wang@merck.com
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
mesh_terms: 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
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019821:Simvastatin