Li W Y, Chatterjee D J, Shetty B V, Wu E Y, Muggia F, Koda R T
Department of Pharmaceutical Sciences, School of Pharmacy, University of southern California, Los Angeles 90033, USA.
J Chromatogr B Biomed Appl. 1995 Nov 17;673(2):281-8. doi: 10.1016/0378-4347(95)00271-4.
AG 331 is a novel thymidylate synthase inhibitor currently in Phase I clinical trial. To determine the pharmacokinetic parameters of AG 3331 in human subjects, a suitable analytical method was developed using high-performance liquid chromatography. Serum and urine samples were prepared using both solid-phase extraction and solvent extraction. Either 4,4'-diaminodiphenyl sulfone or benz[cd]indole-2(1H)-one were used as internal standards for the method. A reversed-phase C18 analytical column completely resolved the drug and internal standard peaks from non-specific substances present in biological matrix. The method was validated for precision, accuracy, and reproducibility in serum and was linear over a concentration range of 50-2000 ng/ml, with a limit of detection of 20.0 ng/ml and a quantifiable limit of 50 ng/ml.
AG 331是一种新型胸苷酸合成酶抑制剂，目前正处于I期临床试验阶段。为了确定AG 3331在人体受试者中的药代动力学参数，开发了一种使用高效液相色谱的合适分析方法。血清和尿液样本采用固相萃取和溶剂萃取两种方法制备。4,4'-二氨基二苯砜或苯并[cd]吲哚-2(1H)-酮用作该方法的内标。反相C18分析柱完全分离了药物和内标峰与生物基质中存在的非特异性物质。该方法在血清中的精密度、准确度和重现性方面得到验证，在50-2000 ng/ml的浓度范围内呈线性，检测限为20.0 ng/ml，定量限为50 ng/ml。
