高效液相色谱法测定大鼠血浆中芳香异羟肟酸二丁基锡的含量以及它在动力学研究中的应用

[(n-Bu)2Sn[{4-ClC6H4C(O)NHO}2] (DBDCT) 是课题组自主设计合成的一种新型芳香异羟肟酸二丁基锡化合物(已获国际国内发明专利),有较高的体内和体外抗肿瘤活性,小鼠急毒实验揭示其具有较低的毒性作用，初步动物实验提示DBDCT还具有升高白细胞的功能，在肿瘤化疗治疗中将产生重要的影响。本文首次建立了HPLC法测定化合物在血浆中的动力学参数。用甲醇直接沉淀血浆蛋白，乙酰苯胺为内标， Diamonsil ODS（4.6 mm × 200 mm, 5 μm）色谱柱，甲醇:0.5%三氟乙酸水溶液（30:70，pH 3.0，v/v）为流动相，检测波长238 nm。方法在0.1～25 µg·mLl-1范围内线性关系良好(r = 0.9992)，定量限和检测限分别为50 和10 ng·mL-1。该方法用来测定单次静脉注射不同剂量(2,5,12mg·kg-1) DBDCT后大鼠体内的浓度-时间曲线，并采用3p97软件对动力学参数和房室模型进行估计，结果表明DBDCT在大鼠体内的动力学符合二室模型，方法简便快速，专属性好，其动力学研究中的应用为制剂的质量控制和临床前动物合理用药以及临床研究提供了实验基础。

An HPLC Method for Determination of a New Diorganotin(IV) Benzohydroxamate in Rat Plasma and Its Application to Pharmacokinetic Studies

[(n‐Bu)₂Sn{4‐ClC₆H₄C(O)NHO}₂] (DBDCT) is a new diorganotin(IV) benzohydroxamate which shows high in vivo antitumor activity with relative low toxicity. An HPLC method for the determination of diorganotin(IV) benzohydroxamate (DBDCT) was first validated in the pharmacokinetic studies in plasma. The rat plasma was deproteinized with methanol that contained acetanilide as the internal standard and then separated. The HPLC assay was carried out using a Diamonsil ODS (4.6 mm×200 mm, 5 µm) column. The mobile phase was methanol and 0.5% trifluoroacetic acid (TFA) in water (30:70, V/V, pH 3.0) with a flow rate of 1.0 mL·min^?1. The detection wavelength was set at 238 nm. This method was found to be linear within the concentration range of 0.1–25 ??g·mL^?1 (r=0.9992). The limit values of quantification and detection were 50 and 10 ng·mL^?1, respectively. The method was used to determine the concentration‐time profiles for DBDCT in the plasma after single intravenous administration with different doses to rats (2, 5, 12 mg·kg^?1). The pharmacokinetics parameter calculations and modeling were carried out using the 3p97 pharmacokinetics software. The results showed that the concentration‐time curve of DBDCT in rat plasma could be fitted to the two‐component model.