Identification and Kinetics Study on the Transformation of Mevinolin in Acidic Alcohol Solution by High-performance Liquid Chromatography with Photodiode Array Detector or Mass Spectrometry

摘要

Mevinolin is one of the earlier statin drugs which is effective for the treatment of hypercholesterolemia, as an inhibitor of the HMG-CoA reductase. The transformations of mevinolin in acidic alcohol(such as ethanol, methanol and isopropanol) solutions caused by solvent effects were revealed in the present article. The solvates, that is, mevinolinic methyl ester, mevinolinic ethyl ester and mevinolinic isopropyl ester, were identified by LC/PDA and LC/MS. The kinetics parameters of the transformations caused by solvent effects, such as the observed rate constant of mevinolin(k_ obs ), the maximum concentration(c_ max ), and its corresponding maximum time(t_ max , time for the acid form to reach the maximum concentration) of mevinolinic acid, are discussed. The influencing factors, such as the kind of solvents, the acidic concentration, the initial mevinolin concentration, and the water content as well as temperature were investigated. Two kinds of comparative reactions, hydrolysis and alcoholysis, of mevinolin in solution were studied. This detailed study on the kinetics of mevinolin transformations is valuable and meaningful for the purification, preparation, injection manufacturing, extraction, storage, etc., of mevinolin or other similar compounds. This work provides useful information for the quality control of mevinolin and mevinolin-like drugs as well.