本文關(guān)鍵詞： 法莫替丁 LC/MS/MS 人血漿 生物等效性　出處：《復(fù)旦學(xué)報(醫(yī)學(xué)版)》2015年04期 　論文類型：期刊論文

【摘要】：目的建立快速靈敏的液相色譜-質(zhì)譜聯(lián)用(LC/MS/MS)法測定人血漿中法莫替丁的含量,并比較兩種法莫替丁膠囊在健康人體內(nèi)的藥動學(xué)及生物等效性。方法血漿樣品中的蛋白經(jīng)甲醇白沉淀處理后,采用LC/MS/MS系統(tǒng)分析,色譜柱為Venusil XBP苯基樁(100 mm×2.1 mm,5μm),以0.1%甲酸水溶液-甲醇(體積分?jǐn)?shù)為60∶40)為流動相,通過電噴霧離子化四級桿串聯(lián)質(zhì)譜,以多反應(yīng)監(jiān)測(multiple-reaction monitoring,MRM)方式進(jìn)行檢測;采用DAS 2.1.1軟件進(jìn)行藥動學(xué)參數(shù)的數(shù)據(jù)處理。結(jié)果此法在標(biāo)準(zhǔn)曲線范圍2.5~250.0ng/mL(r=0.999 9)內(nèi)線性良好,最低定量限為2.5 ng/mL;定量限、低、中、高濃度的方法回收率為97.23%~99.64%,批內(nèi)和批間精密度RSD值為2.30%~4.32%,且提取回收率穩(wěn)定并均大于80%;基質(zhì)效應(yīng)為89.01%~95.73%。兩種膠囊的血藥濃度-時間曲線基本一致,主要藥動學(xué)參數(shù)cmax、AUC0-t、AUC0-∞差異均無統(tǒng)計學(xué)意義,tmax經(jīng)非參數(shù)法檢驗差異無統(tǒng)計學(xué)意義。結(jié)論采用此方法測定血漿藥物濃度時,靈敏度高、準(zhǔn)確度和精密度好,樣品處理簡單,分析測試速度快;試驗?zāi)z囊的相對生物利用度為91.5%±24.5%(n=23,AUC0~t)或90.7%±24.5%(n=23,AUC0~∞),統(tǒng)計分析表明兩種膠囊生物等效。
[Abstract]:Objective to establish a rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) method for the determination of famotidine in human plasma. The pharmacokinetics and bioequivalence of two kinds of famotidine capsules in healthy volunteers were compared. Methods the proteins in plasma samples were treated by methanol white precipitation and analyzed by LC/MS/MS system. The chromatographic column was Venusil XBP phenyl piling (100mm 脳 2.1mm ~ 5 渭 m). The mobile phase consisted of 0.1% formic acid aqueous solution and methanol (60: 40) as mobile phase. The method of electrospray ionization four-pole tandem mass spectrometry was used to monitor multiple-reaction monitoring. DAS 2.1.1 software was used to process the data of pharmacokinetic parameters. Results this method has good linearity in the standard curve range of 2.5 ~ 250.0ng / mLL ~ (0.999 ~ 9). The lowest quantitative limit is 2.5 ng / mL; The recovery rate of high concentration was 97.23 ~ 99.64, the RSD value of intra- and inter-assay precision was 2.30 and 4.322.The recovery was stable and greater than 80, the matrix effect was 89.01 and 95.73.The plasma concentration-time curves of the two capsules were basically the same. There was no significant difference in the main pharmacokinetic parameters (cmaxAX AUC0-tAUC 0- 鈭，

本文編號：1520033