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• 영문명: Quantitative Analysis of Lovastatin in Human Plasma and Urine by Reversed-Phase High-Performance Liquid Chromatography
• 발행기관: 대한약학회
• 저자명: 최혜진(Hye Jin Choi) 김명민(Myoung Min Kim) 최경업(Kyung Eob Choi)
• 간행물 정보: 『약학회지』제42권 제5호 (1998년), 473~479쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1998.10.31

영문 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 hypercholesterolemia, 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 C18 analytical column with a mobile phase containing 0.025M NaH2PO4: 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 0.5mcg/ml while extraction efficiency of LOVA ranged from 73.4-82.9% at LOVA concentrations of 0.5 to 10mcg/ml. Good linearity with correlation coefficients greater than 0.999 was obtained in the range of LOVA concentrations from 0.5 to 10mcg/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, 10mcg/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.

키워드

Lovastatin high-dose therapy HPLC human plasma urine samples.