title: A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching.
abstract: Lovastatin is an anti-cholesterol lactone drug indicated for the treatment of hyperlipidemia and to reduce the risk of coronary heart disease. It is converted to the β-hydroxy acid form (lovastatin acid)in vivo, which is the major pharmacologically active metabolite. Here, we describe the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based method utilizing polarity switching for the simultaneous quantification of lovastatin and lovastatin acid in human plasma. Simple protein precipitation extraction and direct injection of the extracted samples without drying/reconstitution showed good recoveries of both analytes (~70%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The interconversion between lovastatin and lovastatin acid during sample preparation and storage was minimal (< 1.9%). The lower limits of quantification were 0.5 and 0.2 nM (or 0.2 and 0.084 ng/mL) for lovastatin and lovastatin acid, respectively, using only 50 μL of plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving lovastatin.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Wujian
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Kuan-Wei
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sihyung
authors.affiliation: Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Sun
authors.initials: S
authors.lastname: Huijing
authors.affiliation: Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Sampson
authors.initials: S
authors.lastname: Mario
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, USA.
authors.forename: Wang Michael
authors.initials: WM
authors.lastname: Zhuo
keywords: Lovastatin; Lovastatin acid; Pharmacokinetics; Polarity Switching; Protein precipitation extraction; UPLC-MS/MS