کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7616262 | 1494035 | 2016 | 21 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
An HPLC-MS method for the quantification of new acetylcholinesterase inhibitor PC 48 (7-MEOTA-donepezil like compound) in rat plasma: Application to a pharmacokinetic study
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کلمات کلیدی
LLOQRSDFDAtime to CmaxLLEλzTHAtmaxSPEPPTCmaxACNCASHPLC–MS/MS - HPLC-MS / MSUS Food and Drug Administration - اداره غذا و داروی ایالات متحدهSolid phase extraction - استخراج فاز جامدLiquid–liquid extraction - استخراج مایع مایعAcetonitrile - استونیتریلrelative standard deviation - انحراف استاندارد نسبیProtein precipitation - باران پروتئینAlzheimer disease - بیماری آلزایمرTacrine - تاکرینclearance - ترخیص کالا از گمرکmaximal plasma concentration - حداکثر غلظت پلاسماPeripheral anionic site - سایت آنیونی محیطیcatalytic anionic site - سایت آنیونی کاتالیزورlimit of quantitation - محدودیت مقدارelimination rate constant - نرخ ثابت حذفquality control samples - نمونه های کنترل کیفیتPAS - نه
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
A simple, rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative determination in rat plasma of a new candidate for AD treatment, namely PC 48 (a 7-MEOTA-donepezil like compound) in rat plasma. Sample preparation involved pH adjustment with sodium hydroxide followed by solvent extraction with ethyl acetate:dichloromethane (80:20, v/v). The chromatographic separation was achieved on an Ascentis Express RP-Amide column (75 mm Ã 2.1 mm, 2.7 μm) with a gradient mobile phase consisting of 0.05 M aqueous formic acid and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry on an LTQ XL system using the MS/MS CID (collision-induced dissociation) mode. The method was linear in the range 0.1-1000 ng/ml (r2 = 0.999) with a lower limit of quantitation of 0.1 ng/mL. Extraction recovery was in the range 63.5-72.1% for PC 48 and 70.5% for reserpine (internal standard, IS). Intra- and inter-day precisions measured as relative standard deviation were below 10.8% and accuracy was from â7.2% to 7.4%. The method was successfully applied to a pharmacokinetic study involving intramuscular application of 3.86 mg/kg PC 48 to rats for the first time. Pharmacokinetic parameters for PC 48 include Cmax 39.09 ± 4.45 ng/mL, Tmax 5.00 ± 3.08 min, AUC0 â t 23374 ± 4045 min ng/mL and t1/2 1065 ± 246 min.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 1020, 1 May 2016, Pages 85-89
Journal: Journal of Chromatography B - Volume 1020, 1 May 2016, Pages 85-89
نویسندگان
Martin Mzik, Jan Korabecny, Eugenie Nepovimova, Viktor VoÅÃÅ¡ek, Vladimir PaliÄka, Kamil Kuca, Jana Zdarova Karasova,