实用药物与临床
實用藥物與臨床
실용약물여림상
PRACTICAL PHARMACY AND CLINICAL REMEDIES
2014年
5期
598-602
,共5页
EXH-1626%液质联用%大鼠血浆浓度%药代动力学
EXH-1626%液質聯用%大鼠血漿濃度%藥代動力學
EXH-1626%액질련용%대서혈장농도%약대동역학
EXH-1626%LC/MS%Concentration in rat plasma%Pharmacokinetics
目的：建立大鼠血浆中EXH-1626的LC-MS定量分析方法,并运用于大鼠体内EXH-1626的药代动力学研究。方法色谱柱为汉邦ODS C18柱(150 mm ×4．6 mm,5μm),流动相为乙腈-10 mmol/L醋酸铵水溶液(用乙酸调pH至3)70∶30,流速为0．6 mL/min；质谱用ESI离子源及选择性离子监测( SIM)。血浆样品加入内标卡马西平,经蛋白沉淀剂沉淀血浆蛋白,测定EXH-1626的血药浓度,数据经BAPP2．2软件拟合处理,分别考察2个剂量下灌胃和静脉注射给药后,大鼠体内的药代动力学特征。结果血浆中EXH-1626在5~10000 ng/mL范围内线性关系良好(r=0．9997),方法学回收率、精密度、稳定性等均符合要求。大鼠灌胃给药(80 mg/kg)后,其血药浓度-时间过程符合一室模型(W=1),t1/2为24．14 h、Cmax为222．33 ng/mL、Tmax为5．50 h,当大剂量灌胃给药(250 mg/kg)时,大鼠体内药时曲线呈现多峰曲线,药动学过程呈现明显的非线性特征；大鼠尾静脉注射给药(10和20 mg/kg)后体内药时过程也符合一室模型(W =1),t1/2分别为2．23和5．48 h、血浆清除率( CL)分别为0．29和0．08 L/( h·kg)。结论 EXH-1626在大鼠体内存在饱和非线性动力学,所建立的方法快速、准确、灵敏度高,适用于EXH-1626血药浓度测定及其非临床药代动力学研究。
目的：建立大鼠血漿中EXH-1626的LC-MS定量分析方法,併運用于大鼠體內EXH-1626的藥代動力學研究。方法色譜柱為漢邦ODS C18柱(150 mm ×4．6 mm,5μm),流動相為乙腈-10 mmol/L醋痠銨水溶液(用乙痠調pH至3)70∶30,流速為0．6 mL/min；質譜用ESI離子源及選擇性離子鑑測( SIM)。血漿樣品加入內標卡馬西平,經蛋白沉澱劑沉澱血漿蛋白,測定EXH-1626的血藥濃度,數據經BAPP2．2軟件擬閤處理,分彆攷察2箇劑量下灌胃和靜脈註射給藥後,大鼠體內的藥代動力學特徵。結果血漿中EXH-1626在5~10000 ng/mL範圍內線性關繫良好(r=0．9997),方法學迴收率、精密度、穩定性等均符閤要求。大鼠灌胃給藥(80 mg/kg)後,其血藥濃度-時間過程符閤一室模型(W=1),t1/2為24．14 h、Cmax為222．33 ng/mL、Tmax為5．50 h,噹大劑量灌胃給藥(250 mg/kg)時,大鼠體內藥時麯線呈現多峰麯線,藥動學過程呈現明顯的非線性特徵；大鼠尾靜脈註射給藥(10和20 mg/kg)後體內藥時過程也符閤一室模型(W =1),t1/2分彆為2．23和5．48 h、血漿清除率( CL)分彆為0．29和0．08 L/( h·kg)。結論 EXH-1626在大鼠體內存在飽和非線性動力學,所建立的方法快速、準確、靈敏度高,適用于EXH-1626血藥濃度測定及其非臨床藥代動力學研究。
목적：건립대서혈장중EXH-1626적LC-MS정량분석방법,병운용우대서체내EXH-1626적약대동역학연구。방법색보주위한방ODS C18주(150 mm ×4．6 mm,5μm),류동상위을정-10 mmol/L작산안수용액(용을산조pH지3)70∶30,류속위0．6 mL/min；질보용ESI리자원급선택성리자감측( SIM)。혈장양품가입내표잡마서평,경단백침정제침정혈장단백,측정EXH-1626적혈약농도,수거경BAPP2．2연건의합처리,분별고찰2개제량하관위화정맥주사급약후,대서체내적약대동역학특정。결과혈장중EXH-1626재5~10000 ng/mL범위내선성관계량호(r=0．9997),방법학회수솔、정밀도、은정성등균부합요구。대서관위급약(80 mg/kg)후,기혈약농도-시간과정부합일실모형(W=1),t1/2위24．14 h、Cmax위222．33 ng/mL、Tmax위5．50 h,당대제량관위급약(250 mg/kg)시,대서체내약시곡선정현다봉곡선,약동학과정정현명현적비선성특정；대서미정맥주사급약(10화20 mg/kg)후체내약시과정야부합일실모형(W =1),t1/2분별위2．23화5．48 h、혈장청제솔( CL)분별위0．29화0．08 L/( h·kg)。결론 EXH-1626재대서체내존재포화비선성동역학,소건립적방법쾌속、준학、령민도고,괄용우EXH-1626혈약농도측정급기비림상약대동역학연구。
Objective To establish a LC-MS method to quantify EXH-1626 in rat plasma and study its phar-macokinetics. Methods The analysis was conducted with a Han Bang ODS C18 (150 mm × 4. 6 mm,5 μm) column. The mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (using acetic acid makes pH to 3) (70∶30),at a flow rate of 0. 6 mL/min. ESI and SIM were used for MS. Using carbamazepine as internal standard,plasma samples were deposited by blood precipitation reagent before sampling. The concentrations of EXH-1626 in rat blood were determined and processed by BAPP2. 2 program. The method was applied to analyze the dynamic process in the body by giving rats i. g. and i. v. two different doses,respectively. Results The linearity of EXH-1626 concentration curve was in a range of 5~1. 0 × 104 ng/mL,r=0. 999 7,the precision,extraction recovery and stability limit of this method met the requirements of pharmacokinetic study. The mean plasma concentrations of EXH-1626 after i. g. 80 mg/kg EXH-1626 in rats could be fitted to a one-compartment model with a weigh of 1. t1/2 was 24. 14 h,Cmax was 222. 33 ng/mL,and Tmax was 5. 50 h. While giving the large dose(250 mg/kg),it showed multi-peak curve,the phar-macokinetic process had obvious nonlinear characteristic. While after i. v. 10 and 20 mg/kg EXH-1626 in rats,it could be also fitted to a one-compartment model with a weigh of 1. t1/2 were 2. 23 and 5. 48 h,plasma clearances were 0. 29 and 0. 08 L/(h·kg),respectively. Conclusion EXH-1626 exhibits nonlinear pharmacokinetics characteristics in rat. The method is fast,precise and sensitive,and suitable for determination concentration and non-clinical pharmacokinetic study of EXH-1626.
