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

Wujian, J.; Kuan-Wei, P.; Sihyung, Y.; Huijing, S.; Mario, S.; Zhuo, W.M.

Journal of Chromatography and Separation Techniques 6(3): 268

2015


ISSN/ISBN: 2157-7064
PMID: 26146590
DOI: 10.4172/2157-7064.1000268
Accession: 057044195

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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.