RESUMO
OBJECTlVE To develop an LC-MS/MS method for simultaneous determination of pro-damine ( PDM) and its metabolite 2,4-dinitro-N3-propyl-6-trifluoromethyl-1,3-benzenediamine ( DTB) in rat plasma in order to study toxicokinetics of PDM in rats. METHODS SD male rats were administered a single dose of PDM ( ig: 100 and 1000 mg·kg-1; iv: 100 mg·kg-1 ) . LC-MS/MS method was used to determine PDM and DTB in rat plasma. Toxicokinetic parameters were fitted using DAS Ver2. 1. 1. RESULTS After ig administration of PDM 100 mg·kg-1 , the parameters of PDM and DTB were as fol-lows:AUC(0-t) was 2715±102 and (6845±316)μg·h·L-1, t1/2z was 9.0±1.4 and (7.1±1.3)h, Tmax was 7.0± 1.6 and (7.0±0.0)h, cmax was 146±51 and (473±103)μg·L-1. After ig administration of PDM 1000 mg·kg-1, the parameters of PDM and DTB were as follows:AUC(0-t) was 3401±242 and (10364± 573)μg·h·L-1, t1/2z was 8.8±2.1 and (6.0±1.8)h, Tmax was (7.0±1.6)h, cmax was 175±56 and (586± 152)μg·L-1 . The absolute bioavailability of PDM was 44.9%( 100 mg·kg-1 ) and 17.1%( 1000 mg·kg-1 ) . CONCLUSlON This method is suitable for the analysis of PDM and DTB in rat plasma. There is evidence that PDM and DTB display nonlinear toxicokinetic characteristics in the studied dose range.