中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
8期
1171-1174
,共4页
武玉洁%王夙博%袁天翊%李人则%焦晓臻%谢平%方莲花%杜冠华
武玉潔%王夙博%袁天翊%李人則%焦曉臻%謝平%方蓮花%杜冠華
무옥길%왕숙박%원천익%리인칙%초효진%사평%방연화%두관화
DL0805-1%吲唑类化合物%Rho激酶%高效液相色谱法%血药浓度%药代动力学
DL0805-1%吲唑類化閤物%Rho激酶%高效液相色譜法%血藥濃度%藥代動力學
DL0805-1%신서류화합물%Rho격매%고효액상색보법%혈약농도%약대동역학
DL0805-1%indazoles%Rho kinase%HPLC%plasma concentration%pharmacokinetics
目的：建立一种高效液相色谱法( high performance liq-uid chromatography, HPLC)测定具有Rho激酶抑制作用的吲唑类化合物DL0805-1在大鼠血浆中血药浓度的方法,并用该法研究DL0805-1的药物代谢动力学。方法检测系统为Agilent 1200-DAD；色谱柱：Agilent TC-C18(4.6 mm ×250 mm,5μm)；检测波长：235 nm；柱温：35℃；流速：1 ml · min-1；流动相：乙腈与0.05% H3 PO4梯度洗脱；尾静脉给予大鼠DL0805-1,于不同时间点取血,测定血浆中DL0805-1的浓度并计算其药物代谢动力学参数。结果尾静脉给予DL0805-1后,在血浆中检测到原型及其代谢产物。其中, DL0805-1的半衰期为(2.34±1.42) h,达峰浓度为(3.51±0.44)mg·L-1,代谢产物半衰期为(1.27±0.45)h,达峰浓度为(3.55±0.22)mg·L-1。结论 DL0805-1在体内可能代谢成其它物质发挥生物学作用。该法灵敏度高,操作简便、准确,可用于大鼠血浆中DL0805-1的测定及药动学研究。
目的：建立一種高效液相色譜法( high performance liq-uid chromatography, HPLC)測定具有Rho激酶抑製作用的吲唑類化閤物DL0805-1在大鼠血漿中血藥濃度的方法,併用該法研究DL0805-1的藥物代謝動力學。方法檢測繫統為Agilent 1200-DAD；色譜柱：Agilent TC-C18(4.6 mm ×250 mm,5μm)；檢測波長：235 nm；柱溫：35℃；流速：1 ml · min-1；流動相：乙腈與0.05% H3 PO4梯度洗脫；尾靜脈給予大鼠DL0805-1,于不同時間點取血,測定血漿中DL0805-1的濃度併計算其藥物代謝動力學參數。結果尾靜脈給予DL0805-1後,在血漿中檢測到原型及其代謝產物。其中, DL0805-1的半衰期為(2.34±1.42) h,達峰濃度為(3.51±0.44)mg·L-1,代謝產物半衰期為(1.27±0.45)h,達峰濃度為(3.55±0.22)mg·L-1。結論 DL0805-1在體內可能代謝成其它物質髮揮生物學作用。該法靈敏度高,操作簡便、準確,可用于大鼠血漿中DL0805-1的測定及藥動學研究。
목적：건립일충고효액상색보법( high performance liq-uid chromatography, HPLC)측정구유Rho격매억제작용적신서류화합물DL0805-1재대서혈장중혈약농도적방법,병용해법연구DL0805-1적약물대사동역학。방법검측계통위Agilent 1200-DAD；색보주：Agilent TC-C18(4.6 mm ×250 mm,5μm)；검측파장：235 nm；주온：35℃；류속：1 ml · min-1；류동상：을정여0.05% H3 PO4제도세탈；미정맥급여대서DL0805-1,우불동시간점취혈,측정혈장중DL0805-1적농도병계산기약물대사동역학삼수。결과미정맥급여DL0805-1후,재혈장중검측도원형급기대사산물。기중, DL0805-1적반쇠기위(2.34±1.42) h,체봉농도위(3.51±0.44)mg·L-1,대사산물반쇠기위(1.27±0.45)h,체봉농도위(3.55±0.22)mg·L-1。결론 DL0805-1재체내가능대사성기타물질발휘생물학작용。해법령민도고,조작간편、준학,가용우대서혈장중DL0805-1적측정급약동학연구。
Aim ToestablishthemethodofHighper-formance liquid chromatography ( HPLC ) for detecting plasma concentration of indazole compound DL0805-1 , a Rho kinase inhibitor, and to investigate its pharma-cokinetics in rats with intravenous injection. Methods ThedetectingsystemwasAgilent1200-DAD;chro-matographic column was Agilent TC-C18 ( 4. 6 mm × 250 mm, 5 μm); the ultraviolet detection wavelength was 235 nm; the column temperature was 35 ℃; the flow rate was 1 ml·min-1;the mobile phase was ace-tonitrile-0. 05% H3 PO4 gradient elute. Rat blood sam-ples were collected at different intervals after intrave-nous injection of a single dose of DL0805-1 , and the concentration of DL0805-1 in rat plasma were deter-mined by HPLC method for estimating pharmacokinetic parameters.Results Afterintravenousinjectionof DL0805-1 in rats, prototype and its metabolite were detected in plasma. T1/2 of DL0805-1=(2. 34 ± 1. 42) h, Cmax=(3. 51 ± 0. 44) mg·L-1, T1/2 of metabolite of DL0805-1 = ( 1. 27 ± 0. 45 ) h, Cmax = ( 3. 55 ± 0.22)mg·L-1.Conclusion Theseresultssuggest that DL0805-1 may be metabolized into another sub-stance in vivo and play biological functions. The meth-od is sensitive, simple, and accurate, and can be used for the determination of DL0805-1 in rat plasma and pharmacokinetic studies.
