目的 建立人血浆中洛伐他汀的HPLC-ESI-MS 测定法, 以测定志愿者口服洛伐他汀胶囊(20 mg/粒) 后的血药浓度, 并对受试制剂和参比制剂的生物等效性进行评价.方法 20 名健康志愿者交叉口服供试胶囊和参比胶囊, 剂量均为40 mg.采用HPLC-ESI-MS 法测定人血浆中洛伐他汀浓度.采用BAPP2.0软件计算主要药动学参数及相对生物利用度.结果 在0.5 ～ 30 ng·mL-1范围内,洛伐他汀和内标辛伐他汀的峰面积比值与浓度线性关系良好, 最低定量限为0.5 ng·mL-1 .受试制剂及参比制剂的t1/2分别为(6.02 ± 1.67) h 和(5.63 ± 1.00) h , Tmax分别为(2.8 ± 0.5) 和(2.7 ± 0.4) h , Cmax分别为(14.58 ± 4.55) 和 (14.38 ± 4.51) ng·mL-1.以AUC0 - 24计算的受试制剂的相对生物利用度为(95.9 ± 14.4) %. 结论 本实验建立的人血浆中洛伐他汀HPLC-MS 分析方法简便,且灵敏、准确.统计学结果表明两种洛伐他汀制剂生物等效.“,”Aim To establish a sensitive and specific liquid chromatography-mass spectrometry (HPLC-MS) method for measuring lovastatin level in human plasma and the relative bioavailability. Methods Lovastatin in the plasma was extracted with acetoacetate. Simvastatin was added as internal standard (IS). Samples were separated on a C18 column with a mobile phase consisting of methanol and 50 mmol·L-1 sodium acetate (88∶12). The flow rate was 1 mL·min-1. Sample was detected using an electrospray ionization (ESI) mass spectrometer with selected ion monitoring (SIM) and positive-ionization mode. The target ionsat for lovastatin was m/z 427.3, while that for simvastatin was m/z 441.3. The fragmentor voltage was 150 V. A randomized crossover study was performed in 20 healthy Chinese male volunteers. In the two study periods, each subject was given orally two capsules at a single dose 40 mg of lovastatin. Results The calibration curve was linear in the range of 0.5 - 30 ng·mL-1. The limit of quantification was 0.5 ng·mL-1. The parameters for lovastatin test capsule and reference capsule were as follows: T1/2 (6.02 ± 1.67) and (5.63±1.00) h, Tmax (2.8 ± 0.5) and (2.7 ± 0.4) h, Cmax (14.58 ± 4.55) and (14.38 ± 4.51) ng·mL-1, respectively. The relative bioavailability was 95.9 %±14.4 %. Conclusion The established HPLC-MS method is rapid, sensitive and specific for determination of lovastatin level in human plasma.