Detection of 4a,5-dihydropravastatin as Impurity in the Cholesterol Lowering Drug Pravastatin

Abstract

Dihydro analogues are known byproducts of the fermentative production of statins and cannot be detected with existing pharmacopoeia analysis methods. We detected dihydropravastatin in most commercial formulations of pravastatin with LC-MS, in some cases in levels requiring identification. In fermentation broth samples of the single step production of pravastatin, we detected and identified for the first time 4a,5-dihydropravastatin, and confirmed that after several recrystallization steps this impurity can be fully removed from the pravastatin powder.

Keywords

• dihydrostatins
• biosynthesis
• finished dosage forms
• active pharmaceutical ingredient
• mass spectrometry
• NMR