초록
Lovastatin (LOVA), a fungal metabolite isolated from cultures of Aspergillus terreus, is a competitive HMG-CoA reductase inhibitor used for the treatment of primary hyper cholesterolemia, and has also been shown to suppress growth in a variety of non-glioma tumor cell lines. A sensitive reversed-phase high-perfonnance liquid chromatographic method with ultraviolet (UV) absorbance detection has been developed to quantitate LOVA in human plasma and urine samples using liquid-liquid extraction procedure. Baseline separation of LOVA and internal standard, simvastatin was achieved on a Novapak $C_{18}$ analytical column with a mobile phase containing 0.025M $NaH_2PO_4$: CAN (35:65, v/v%), adjusted pH to 4.5. The flow rate was set at 1.5ml/min, and the column effluent was monitored by a UV detection at 238nm. The limit of quantification was determined to be 0.5${\mu}$g/ml while extraction efficiency of LOVA ranged from 73.4-82.9% at LOVA concentrations of 0.5 to 10${\mu}$g/ml. Good linearity with correlation coefficients greater than 0.999 was obtained in the range of LOVA concentrations from 0.5 to 10${\mu}$g/ml. The accuracy and the precision were proven excellent with relative standard deviation (RSD, %) and relative error (RE, %) of less than 4.2 and 4.0, respectively. Intraday precision, evaluated at five LOVA concentrations (0.5, 1, 2, 5, 10${\mu}$g/ml) and expressed as RSD ranged from 0-1.82% while the interday precision at the same concentrations ranged from 0.7-10.5%. The analytical method described was then successfully employed for the determination of LOVA concentrations in plasma samples obtained during a phase II clinical trial using high doses of LOVA (30-40mg/kg/day). This method could be further utilized for the ongoing pharmacolkinetic studies and therapeutic drug monitoring of the high-dose LOVA therapy in adenocarcinoma patients.