Development of a Highly Sensitive and Selective LC-MS/MS Method that Allows the Differentiation of Pravastatin from its Major Isomeric Metabolites

摘要

Pravastatin (PV) is a lipid-lowering drug used to reduce cholesterol biosynthesis, and is rapidly absorbed with peak plasma levels of parent compound attained 1 to 1.5 hours following oral administration. In vivo, PV is metabolized through isomerization to an active metabolite 3-(alpha)-iso-Pravastatin (3-(alpha)-iso-PV) and an inactive metabolite 6-epi-pravastatin (6-epi-PV) (Fig.1). All above three analytes have the same mass and generate the same precursor to product ion transitions using tandem mass spectrometry, and therefore cannot be differentiated by mass spectrometry alone. Our work reported here has achieved an excellent chromatographic separation of the three analytes. A series of tests were also performed to establish and minimize any interconversion between PV and its isomeric metabolites during the assay procedure.