Bioanalytical LC–MS/MS method for simultaneous estimation of atorvastatin, its major active metabolites and ezetimibe: supplementary data

Background: Hyperlipidemia is one of the most common chronic diseases encountered globally, and
atorvastatin (ATV) is mainly metabolized into two major active metabolites. Methodology: Hence, we
aimed to estimate ATV and ezetimibe (EZE) simultaneously in the presence of ATV major and active
metabolites using a validated LC–MS/MS method. Conclusion: The proposed method was linear (r2 >0.99),
accurate (92.02–109.94%) and precise (CV% ≤14) over the concentration range of 0.50–120 ng/ml, 0.20–
48 ng/ml, 0.50–120 ng/ml and 0.20–48 ng/ml for ATV, EZE, 2-hydroxy ATV and 4-hydroxy ATV, respectively.
The applied liquid–liquid extraction gave rise to reliable extraction recoveries of 84.91 ± 1.14%,
85.20 ± 1.62%, 85.46 ± 0.41% and 105.46 ± 2.35% for ATV, EZE, 2-hydroxy ATV and 4-hydroxy ATV,
respectively.

背景：高脂血症（Hyperlipidemia）是全球范围内最常见的慢性疾病之一，阿托伐他汀（atorvastatin, ATV）主要经代谢生成两种主要活性代谢产物。方法：因此，本研究旨在采用经方法学验证的液相色谱-串联质谱法（LC–MS/MS），在阿托伐他汀主要活性代谢物存在的体系中，同时测定阿托伐他汀与依折麦布（ezetimibe, EZE）的含量。结论：所建立的分析方法线性关系良好（决定系数r²>0.99），准确度为92.02%~109.94%，精密度（变异系数CV%）≤14；其中阿托伐他汀、依折麦布、2-羟基阿托伐他汀及4-羟基阿托伐他汀的线性浓度范围分别为0.50~120 ng/ml、0.20~48 ng/ml、0.50~120 ng/ml及0.20~48 ng/ml。采用液液萃取（liquid–liquid extraction）进行样品前处理，所得阿托伐他汀、依折麦布、2-羟基阿托伐他汀及4-羟基阿托伐他汀的萃取回收率分别为84.91±1.14%、85.20±1.62%、85.46±0.41%及105.46±2.35%，结果可靠。