Asberg Anders, Hansen Christin Nupen, Reubsaet Leon
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Blindern, Oslo, Norway.
J Pharm Biomed Anal. 2007 Feb 19;43(3):1039-44. doi: 10.1016/j.jpba.2006.08.022. Epub 2006 Oct 10.
The aim of the present study was to develop a time-efficient chromatographic method for the analysis of therapeutic concentrations of ganciclovir (GCV) in plasma, urine as well as dialysate (from continuous renal replacement therapy) from solid organ transplant recipient treated with either GCV or its prodrug valganciclovir (VGCV) in combination with a wide variety of other concomitant drugs. Sample preparation was performed by reversed phase solid phase extraction and was followed by separation of the analytes on a reversed phase column using isocratic elution with a mobile phase consisting of acetonitrile-a counter ion (50 mM 1-heptanesulfonic acid) in an aqueous sodium dihydrogen phosphate buffer (pH 2.1; 10 mM) (10:90 v/v) and a fluorescence detector. Validation of the method showed linearity within the concentration range of 0.1-40 microg/mL for plasma and 0.1-120 microg/mL for urine and dialysate (R(2)>0.99, n> or =5). Accuracy and precision (evaluated at 0.1, 5 and 40 microg/mL) were both satisfactory. The LLOQ was determined to be 0.1 microg/mL. The method was successfully applied on clinical samples from renal transplant recipients treated with VGCV in combination with a variety of usually used concomitant drugs for solid organ transplant recipients.
本研究的目的是开发一种高效的色谱方法,用于分析实体器官移植受者血浆、尿液以及透析液(来自持续肾脏替代治疗)中更昔洛韦(GCV)的治疗浓度。这些受者接受了GCV或其前体药物缬更昔洛韦(VGCV)治疗,并同时使用了多种其他伴随药物。样品制备采用反相固相萃取法,然后在反相柱上进行分析物的分离,使用等度洗脱,流动相由乙腈 - 一种抗衡离子(50 mM 1 - 庚烷磺酸)在磷酸二氢钠水溶液缓冲液(pH 2.1;10 mM)(10:90 v/v)中组成,并配备荧光检测器。该方法的验证表明,血浆浓度范围在0.1 - 40 μg/mL、尿液和透析液浓度范围在0.1 - 120 μg/mL内呈线性(R²>0.99,n≥5)。准确度和精密度(在0.1、5和40 μg/mL处评估)均令人满意。最低定量限确定为0.1 μg/mL。该方法成功应用于接受VGCV治疗并同时使用多种实体器官移植受者常用伴随药物的肾移植受者的临床样本。