Abstract: 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: T_1/2 (6.02 ± 1.67) and (5.63 ± 1.00) h, Tmax (2.8 ± 0.5) and (2.7 ± 0.4) h, C_max (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.

Key words: lovastatin, lovastatin, pharmacokinetics, pharmacokinetics, bioavailability, bioavailability, HPLC-MS, HPLC-MS