CAJ | 학술논문

目的：建立大鼠血浆中氨氟乐灵( PDM)及其代谢产物2,4-二硝基-N3-丙基-6-三氟甲基-1,3-苯二胺( DTB )的分析方法,进行氨氟乐灵大鼠体内毒代动力学研究。方法分别采用 ig (100 mg·kg－1,1000 mg·kg－1)和iv(100 mg·kg－1)单次给予雄性SD大鼠PDM,应用液质联用仪(LC-MS/MS)测定大鼠血浆中PDM和DTB的含量,采用DAS软件拟合毒代动力学参数。结果单次ig给予PDM 100 mg·kg－1, PDM和DTB的主要毒代动力学参数分别为：曲线下面积〔AUC(0－t)〕分别为2715±102和(6845±316)μg·h·L－1；半衰期(t1/2z)分别为9.0±1.4和(7.1±1.3)h；达峰时间(Tmax)分别为7.0±1.6和(7.0±0.0)h；峰值浓度(cmax)分别为146±51和(473±103)μg·L－1。单次ig给予PDM 1000 mg·kg－1,PDM和DTB的主要毒代动力学参数分别为：AUC(0－t)分别为3401±242和(10364±573)μg·h·L－1；t1/2z分别为8.8±2.1和(6.0±1.8)h；Tmax均为(7.0±1.6)h；cmax分别为175±56和(586±152)μg·L－1。 PDM 在大鼠体内的绝对生物利用度分别为44.9％(100 mg·kg－1)和17.1％(1000 mg·kg－1)。结论该LC-MS/MS 分析方法适用于大鼠血浆中PDM 和DTB的测定。 PDM和DTB在大鼠体内的毒代动力学过程具有非线性动力学性质。
목적：건립대서혈장중안불악령( PDM)급기대사산물2,4-이초기-N3-병기-6-삼불갑기-1,3-분이알( DTB )적분석방법,진행안불악령대서체내독대동역학연구。방법분별채용 ig (100 mg·kg－1,1000 mg·kg－1)화iv(100 mg·kg－1)단차급여웅성SD대서PDM,응용액질련용의(LC-MS/MS)측정대서혈장중PDM화DTB적함량,채용DAS연건의합독대동역학삼수。결과단차ig급여PDM 100 mg·kg－1, PDM화DTB적주요독대동역학삼수분별위：곡선하면적〔AUC(0－t)〕분별위2715±102화(6845±316)μg·h·L－1；반쇠기(t1/2z)분별위9.0±1.4화(7.1±1.3)h；체봉시간(Tmax)분별위7.0±1.6화(7.0±0.0)h；봉치농도(cmax)분별위146±51화(473±103)μg·L－1。단차ig급여PDM 1000 mg·kg－1,PDM화DTB적주요독대동역학삼수분별위：AUC(0－t)분별위3401±242화(10364±573)μg·h·L－1；t1/2z분별위8.8±2.1화(6.0±1.8)h；Tmax균위(7.0±1.6)h；cmax분별위175±56화(586±152)μg·L－1。 PDM 재대서체내적절대생물이용도분별위44.9％(100 mg·kg－1)화17.1％(1000 mg·kg－1)。결론해LC-MS/MS 분석방법괄용우대서혈장중PDM 화DTB적측정。 PDM화DTB재대서체내적독대동역학과정구유비선성동역학성질。
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.