Ultra-high performance supercritical fluid chromatography-tandem mass spectrometry method for simultaneous determination of atorvastatin, 2-hydroxy atorvastatin, and tangeretin in rat plasma and its application to the pharmacokinetic study.

Recent studies strongly suggest that atorvastatin combination therapy with tangeretin could be beneficial in the treatment of hyperlipidemia. This study aimed to investigate the pharmacokinetic interactions among atorvastatin, its active metabolite 2-hydroxy atorvastatin, and tangeretin after oral administration of atorvastatin with tangeretin in rats. A rapid, selective, and sensitive assay was developed and validated based on ultra-high performance supercritical fluid chromatography-tandem mass spectrometry for the simultaneous measurement of atorvastatin, 2-hydroxy atorvastatin, and tangeretin concentrations in rat plasma. Chromatographic separation of the analytes was conducted on an ACQUITY Torus 1-AA column in gradient elution mode. The mass transition ion pairs were m/z 559.0→440.0 for atorvastatin, m/z 575.2→440.0 for 2-hydroxy atorvastatin, m/z 373.0→358.1 for tangeretin, and m/z 254.8→136.7 for daidzein (internal standard). Calibration curves showed good linear correlations at the following concentration range: 1-400 (r = 0.9952), 1-400 (r = 0.9980), and 3-1200 (r = 0.9945) for atorvastatin, 2-hydroxy atorvastatin, and tangeretin, respectively. The method was fully validated and satisfied the acceptance criteria recommended by the United States Food and Drug Administration. Finally, it was successfully applied in a pharmacokinetic study in rats to evaluate the pharmacokinetic behavior of atorvastatin, 2-hydroxy atorvastatin, and tangeretin.