液相色譜-串聯(lián)質(zhì)譜法測定犬血漿中左旋泮托拉唑鈉的濃度及其毒代動力學(xué)研究
發(fā)布時間:2018-04-15 17:14
本文選題:左旋泮托拉唑鈉 + 犬血漿。 參考:《中國藥學(xué)雜志》2017年15期
【摘要】:目的建立液相色譜-串聯(lián)質(zhì)譜法測定犬血漿中左旋泮托拉唑鈉的濃度并研究其毒代動力學(xué)。方法犬血漿樣本以乙腈沉淀蛋白后,選用CHIRALCEL OJ-RH色譜柱(4.6 mm×150 mm,5μm);流動相為乙腈-水=28∶72,流速為0.6 m L·min~(-1) ,柱溫為35℃;選用Agilent 6430三重四極桿串聯(lián)質(zhì)譜儀,離子化方式:電噴霧-正離子(API-ES),監(jiān)測方式:MRM,左旋泮托拉唑監(jiān)測離子對384.0/199.8,非那西丁監(jiān)測離子對180.0/110.0,用作內(nèi)標(biāo)。結(jié)果本分析方法專屬性良好;左旋泮托拉唑鈉在50~30 000 ng·m L~(-1) 內(nèi)線性關(guān)系符合要求;準(zhǔn)確度均在85%~115%,精密度RSD在15%內(nèi)。Beagle犬連續(xù)4周靜脈注射給予注射用左旋泮托拉唑鈉低、中、高(10、20、40 mg·kg~(-1) ·d~(-1) )3個劑量,左旋泮托拉唑鈉動力學(xué)參數(shù)AUC_(0-4h)和ρ_(max)增長與劑量增長均呈正相關(guān)。首次和4周給藥后測定無明顯差異。結(jié)論本法經(jīng)方法學(xué)驗證,適用于犬血漿中左旋泮托拉唑鈉濃度測定,可用于左旋泮托拉唑鈉犬體內(nèi)毒代動力學(xué)研究。
[Abstract]:Objective to establish the determination of the concentration of - pantoprazole sodium in dog plasma by liquid chromatography tandem mass spectrometry and study the toxicokinetics. Methods canine plasma samples with acetonitrile protein precipitation, using CHIRALCEL OJ-RH column (4.6 mm * 150 mm, 5 m); mobile phase of acetonitrile water =28: 72 the flow rate was 0.6 m L min~ (-1), the column temperature is 35 DEG C; the Agilent 6430 three triple quadrupole tandem mass spectrometer ionization mode: positive electrospray ionization (API-ES), monitoring: MRM, - pantoprazole monitoring ions on 384.0/199.8, phenacetin monitoring ions of 180.0/110.0, as in standard analysis method. Results the specificity is good; the - pantoprazole sodium in the 50~30 000 ng m L~ (-1) linear relationship with the requirements; the accuracy was in 85%~115%, the precision of RSD.Beagle in 15% dogs in 4 consecutive weeks of intravenous injection with levo pantoprazole sodium injection, (low, high 10,20,40 Mg (kg~ -1) - d~ (-1)) 3 doses, the - pantoprazole sodium kinetics parameters of AUC_ (0-4h) and P _ (max) growth and growth are positively correlated. The first dose and 4 weeks after drug administration were no significant difference. Conclusion this method is applicable to the determination of the method validation, the - pantoprazole sodium the concentration in dog plasma, can be used for the - pantoprazole sodium in dogs toxicikinetics.
【作者單位】: 山東省藥學(xué)科學(xué)院;
【分類號】:R965
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