Metals offer potential advantages over the more common organic-based drugs, including a wide range of coordination numbers and geometries, accessible redox states, “tuneability” of the kinetics of ligand substitution, as well as a wide structural diversity. Medicinal inorganic chemistry is a thriving area of research [1
], initially fueled by the discovery of cisplatin, a metal-based antitumor drug about 40 years ago. Since the discovery of cisplatin and its introduction in the clinics, metal compounds have been intensely investigated in view of their possible application in cancer therapy. Platinum anticancer agents, such as cisplatin, have been highly successful but there are several disadvantages associated with their clinical use. What needs to be recognized is that there are many other nonplatin metal-based antitumor drugs in the periodic table with therapeutic potential. Diorganotin(IV) complexes are potential antitumor agents mainly active against P388 lymphocytic leukemia and other tumors [3
]. Lately, these antitumor agents are actually being studied widely. Among diorganotin(IV) compounds, dibutyltin(IV) derivatives of hydroxamic acid have received more attention due to their structural and biological importance [6
Recently, we reported a series of diorganotin(IV) arylhydroxamates which exhibit in vitro
antitumor activities (against a series of human tumor cell lines) which, in some case, are identical to, or even higher than, that of cisplatin
]. Di-phenyl-di-(2,4- difluobenzohydroxamato)tin(IV) (DPDFT, its structure was shown in ), a kind of efficient diorganotin(IV) patent compound (number: ZL01135148 and 102826Z) with lower toxicity, is a potential antitumor candidate for the clinical application due to its high in vivo and in vitro
activity mainly against hepatoma, gastric cancer, nasopharyngeal carcinoma and other tumors (data not shown here). However, its antitumor molecular action mechanism is still unclear. In order to study the precise action mechanism and toxicity of this metal-based antitumor diorganotin(IV) compound, its fate should be first elucidated in vivo
, including their absorption, distribution, metabolism, and elimination. However, nothing is known about the pharmacokinetic behavior of DPDFT in body. Therefore, it is essential to establish a rapid, sensitive, and accurate method to determine the pharmacokinetic of organotin compound DPDFT in a body.
For medical care, practical, robust, simple, and efficient analytical methods are needed. Several methods have been reported for the determination of organotin compounds, including HPLC-MS [9
], HPLC-ICP-MS [10
], GC [12
], GC-MIP AED [12
], GC-MS [15
], GC-ICP MS [18
], and so on. However, these methods have obvious disadvantages. For examples, GC methods have complicated pretreatments for the samples and seem to be unsuitable for quantitative determination in rat plasma because only a small amount of blood is normally used in pharmacokinetic studies. HPLC-MS is superior method and should be used whenever is possible. MS methods were used for mentioned analysis in order to increase selectivity of detection of DPDFT from complex matrixes. However, in this study, the HPLC-MS method was not used because the mass spectrometry conditions were still not ripe for DPDFT detection, and the high analysis cost and the expensive apparatus required were other considerations. So far, to the best of our knowledge, no method has been reported for determination of the diorganotin(IV) patent compound DPDFT by HPLC method with UV detection in the pharmacokinetic studies in rat plasma. Therefore, in this research, we chose DPDFT as a typical antitumor diorganotin(IV) arylhydroxamate to develop a simple, sensitive, and specific HPLC assay for its quantitative determination in rat plasma and to investigate its preliminary pharmacokinetic properties.