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

Abstract

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.

Development and validation of a LC-MS/MS method for the simultaneous determination of cycloicaritin and its carbamate prodrug in rat plasma: application to pharmacokinetic study

“…Chromatographic conditions were optimized to gain better performance in separation, peak shape and response. The chemistry of stationary phase was one of the most important parameters affecting the retention of the compounds, 22,23 and we found that 3-L could easily get good peak shape and appropriate retention time, but CICT was difficult to elute resulting in long retention time and serious peak tailing, so different chromatographic columns were investigated including Waters XBridge TM C 18 column (75 mm × 4.6 mm, 2.5 μm), ACE Excel 2 C 18 -Amide column (50 mm × 2.1 mm, 2 μm), ZORBAX SB-C 8 (50 mm × 2.1 mm, 3.5 μm) and Kinetex® XB-C 18 (50 mm × 2.1 mm, 2.6 μm). The results showed that only ACE Excel 2 C 18 -Amide column with polar embedded amide as stationary phase met the requirement for excellent separation and acceptable peak shape of CICT.…”