Identification of an Impurity in Pravastatin by Apliccation of Collision-Activated Decomposition Mass Spectra

Andrej Kocijan,a Rok Grahek,a Lucija Zupančič-Kralj b

aLek Pharmaceuticals d.d., Development Center Slovenia, Verovškova 57, SI-1526 Ljubljana, Slovenia
b Faculty of Chemistry and Chemical Technology, Aškerčeva 5, SI-1000 Ljubljana, Slovenia

Pravastatin is produced by a two step fermentation. Mevastatin and 6-epi pravastatin are the main impurities in the fermentation broth as well as in final product. An unknown impurity with m/z 437 for (M-H)- was detected in analysis of pravastatin sodium sample by reversed phase HPLC-MS. CAD spectrum of the impurity was obtained using HPLC-MS/MS equipped with negative APCI. The CAD mass spectra of impurity was similar with CAD mass spectra of statins. The structure of an impurity was finally determined on the basis of proposed fragmentation mechanisms for statins.

Keywords: HMG-CoA reductase inhibitors, statins, tandem mass spectrometry, impurity identification