Swynnerton N F, Huelle B K, McGovern E P, Mangold D J, Ludden T M
Res Commun Chem Pathol Pharmacol. 1986 Nov;54(2):255-69.
Described is a high-performance liquid chromatographic (HPLC) method for the quantification of WR-1065 [2-(3-aminopropylamino)-ethanethiol] in plasma. After a brief sample preparation, the drug and internal standard were separated in less than 15 minutes using a reversed-phase column and ion-pairing reagent. An electrochemical detector provided a minimum quantifiable limit of 0.05 microgram/mL. The analytical method was applied in three experiments to measure drug concentrations in the plasma of beagle dogs following IV administration of WR-1065 (60 mg/kg). The concentration-time data, best described by a three-compartment open kinetic model, were used to estimate pharmacokinetic parameters. Mean values were: steady state volume of distribution--2.27 L X kg-1; clearance--0.064 L X min-1 X kg-1; and terminal elimination half-life--81.4 min. The high clearance is consistent with the formation of mixed disulfides in the circulation.
本文描述了一种用于定量血浆中WR-1065[2-(3-氨丙基氨基)-乙硫醇]的高效液相色谱(HPLC)方法。经过简短的样品制备后，使用反相柱和离子对试剂在不到15分钟内将药物和内标分离。电化学检测器的最低可定量限为0.05微克/毫升。该分析方法应用于三个实验，以测量比格犬静脉注射WR-1065(60毫克/千克)后血浆中的药物浓度。浓度-时间数据最适合用三室开放动力学模型描述，用于估算药代动力学参数。平均值为：稳态分布容积——2.27升·千克-1；清除率——0.064升·分钟-1·千克-1；以及末端消除半衰期——81.4分钟。高清除率与循环中混合二硫化物的形成一致。
