Hedaya M A, Sawchuk R J
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Pharm Res. 1990 Nov;7(11):1113-8. doi: 10.1023/a:1015920023272.
A liquid-chromatographic assay for the analysis of ganciclovir in plasma and urine is described. This assay involves the use of acyclovir, an antiviral drug structurally related to ganciclovir, as the internal standard. A two-step sample preparation method is used. After protein is precipitated with acetonitrile and the addition of diethyl ether, ganciclovir and the internal standard are back extracted into a small volume of aqueous ammonium phosphate, taking advantage of their relatively high water solubility. This isocratic method is specific and sufficiently sensitive to allow quantification of ganciclovir throughout the entire range of concentrations observed during therapeutic use of this antiviral drug. There was no interference from various over-the-counter and prescription drugs often prescribed to patients most likely to receive ganciclovir therapy. This assay was used to analyze plasma and urine samples obtained after intravenous administration of ganciclovir to rabbits. Biexponential decay of ganciclovir plasma concentration-time and urinary excretion rate-time profiles was observed, with a mean distribution half-life of 15.8 min and an elimination half-life of 96 min. The mean renal clearance, 9.0 ml/min per kg, exceeds the glomerular filtration rate in the rabbit, indicating that ganciclovir is actively secreted in the renal tubule. Similar results were obtained by determining the renal clearance at steady state during constant-rate intravenous infusion of ganciclovir.
本文描述了一种用于分析血浆和尿液中更昔洛韦的液相色谱测定法。该测定法使用阿昔洛韦作为内标，阿昔洛韦是一种在结构上与更昔洛韦相关的抗病毒药物。采用两步样品制备方法。在用乙腈沉淀蛋白质并加入乙醚后，利用更昔洛韦和内标相对较高的水溶性，将它们反萃取到少量磷酸铵水溶液中。这种等度洗脱方法具有特异性且灵敏度足够高，能够在该抗病毒药物治疗使用期间观察到的整个浓度范围内对更昔洛韦进行定量。各种非处方药和处方药通常不会干扰最有可能接受更昔洛韦治疗的患者。该测定法用于分析给兔子静脉注射更昔洛韦后获得的血浆和尿液样本。观察到更昔洛韦血浆浓度 - 时间和尿排泄率 - 时间曲线呈双指数衰减，平均分布半衰期为15.8分钟，消除半衰期为96分钟。平均肾清除率为每千克每分钟9.0毫升，超过兔子的肾小球滤过率，表明更昔洛韦在肾小管中被主动分泌。在更昔洛韦恒速静脉输注期间通过测定稳态肾清除率也获得了类似结果。
