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.
Keywords: LC–MS/MS; atorvastatin; bioanalysis; ezetimibe; major metabolites; pharmacokinetics.