Abstract: OBJECTIVE To establish a LC-MS/MS method for simultaneous determination of atorvastatin, o-hydroxyatorvastatin and p-hydroxyatorvastatin in rat plasma, and apply to the pharmacokinetic study of atorvastatin in CYP3A-induced model rats and normal rats. METHODS MTBE-ethyl acetate(50︰50) was used to extract the drug in rat plasma in addition to the selection of XBridge C₁₈(2.1 mm×250 mm, 3.5 μm) as the HPLC column. The column was kept at a constant temperature(35℃). The mobile phase was 0.1% formic-acetonitrile(40:60), isocratic elution for 4.4 min at a flow rate of 0.2 mL·min^-1 and the injection volume was 10 μL. The detection of analytes was achieved by tandem mass spectrometry with electrospray ionization(ESI) interface in positive ion mode. The following multiple reaction monitoring(MRM) transitions were selected:m/z 559.1→440.1(atorvastatin), m/z 575.3→440.2(o-hydroxyl atorvastatin/p-hydroxyl atorvastatin), m/z 564.3→445.3 (atorvastatin-d₅, IS). The rats randomly selected as CYP3A-induced models were administrated with an oral dose of 80 mg·kg^-1·d^-1 dexamethasone for 4 d. Blood samples of normal and model rats were collected in heparinized tubes before, and at 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6 h after atorvastatin administration. Plasma was harvested by centrifugation and stored frozen until analysis. RESULTS Atorvastatin and its metabolites showed a wide linear range from 0.49-500.00 ng·mL^-1(r²>0.99). The analytical method presented the RSD of intra-day precision and inter-day precision were <15%(n=6); the extraction recovery and matrix effect satisfied the determination standard for biological samples. Futhermore, the drug contained plasma samples stayed stable in 4, 24 h in room temperature and 3 d in 4℃. In pharmacokinetic parameters, the T_max and AUC_0-t of rats in induced group were lower than those of normal group, while the K and CL were higher. CONCLUSION The newly developed method is convenient, stable and sensitive. It can be applied to the simultaneous determination of atorvastatin and its active metabolites in rat plasma for the pharmacokinetics study. The active atorvastatin components entering the general circulation demonstrated significant differences between the CYP3A-induced model rats and normal rats.