Determination and pharmacokinetics of a new diorganotin(IV) complex dibutyldi(4-chlorobenzohydroxamato)tin(IV) in rat plasma by a high performance liquid chromatographic method.
Dibutyldi(4-chlorobenzohydroxamato)tin(IV) is a new diorganotin(IV) arylhydroxamate complex with 4-chloro-benzohydroxamic acid as ligand which shows high in vivo and in vitro antitumor activity. A high performance liquid chromatographic (HPLC) method using a Diamonsil ODS column was first validated in the pharmacokinetic studies in rat plasma. The plasma was deproteinized with methanol that contained acetanilide as the internal standard. The mobile phase was a mixture of methanol and 0.5% trifluoroacetic acid (TFA) in water (30:70) (pH 3.0). The detection wavelength was set at 238 nm. A linear curve over the concentration range 0.1-25 microg/ml (r = 0.9992) was obtained. The method was used to determine the concentration-time profiles for dibutyldi(4-chlorobenzohydroxamato)tin(IV) in the plasma after a single intravenous dose of 2, 5, and 12 mg/kg to rats. The pharmacokinetics parameter calculations and modeling were carried out using the 3p97 pharmacokinetics software. A nonlinear pharmacokinetics was found in rats at doses from 2 to 12 mg/kg. The results showed that the concentration-time curves of dibutyldi(4-chlorobenzohydroxamato)-tin(IV) in rat plasma could be fitted to two-compartment model.
School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, People's Republic of China.
Yunlan
Y
Li
Jinjie
J
Liu
Yong
Y
Li
Qingshan
Q
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D016014:Linear Models; D008297:Male; D009947:Organotin Compounds / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013997:Time Factors
D000970:Antineoplastic Agents; D009947:Organotin Compounds; C542282:dibutyldi(4-chlorobenzohydroxamato)tin(IV)