Collision‐induced dissociation of the negative ions of simvastatin hydroxy acid and related species

Simvastatin hydroxy acid ( 1 ) is a well‐known, potent HMG‐CoA reductase inhibitor for the treatment of hypercholesterolemia. Its lactone, simvastatin (commercial name Zocor) (a prodrug of 1 ), has been widely prescribed in the USA and throughout the world. In this work, collision‐induced dissociation (CID) of the negative ion of 1 ( m/z 435), a carboxylic anion, was analyzed in detail. The major fragmentation pathway of this ion is a novel de‐esterification to form the negative product ions at m/z 319 and 115. The ion at m/z 319 undergoes further collision‐induced rearrangements to form the negative ions at m/z 215, 159 and 85. Possible mechanisms of the de‐esterification are discussed in terms of both charge‐initiated and charge‐remote fragmentations. The de‐esterification of the negative ion of 1 and the rearrangements of the ion at m/z 319 are rationalized by charge transfer and negative‐charge initiated fragmentation. This study deepens our understanding of collision‐induced fragmentations of carboxylic anions with multi‐functional groups. A comparison of the CID data for the negative ions of 1 and 5 (a major oxidation degradate of 1 ) indicates that the analysis of the CID data for 1 can serve as a basis for identification of oxidation degradation products or metabolites of 1 . The analysis of the CID data for the negative ion of 1 also reveals the fundamental characteristics of the CID data for the negative ions of other statin hydroxy acids such as lovastatin ( 3 ) and pravastatin ( 4 ). Copyright © 2003 John Wiley & Sons, Ltd.