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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875582" target="_blank" >RIV/60162694:G44__/16:43875582 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/16:10324298

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S1570023216301258" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1570023216301258</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jchromb.2016.02.038" target="_blank" >10.1016/j.jchromb.2016.02.038</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 x 2.1 mm, 2.7 mu m) 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 LTQXL system using the MS/MS CID (collision-induced dissociation) mode. The method was linear in the range 0.1-1000 ng/ml(r(2) = 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 -7.2% 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 C-max 39.09 +/- 4.45 ng/mL,T-max 5.00 +/- 3.08 min, AUC(0-t) 23374 +/- 4045 min ng/mL and t(1/2) 1065 +/- 246 min.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 x 2.1 mm, 2.7 mu m) 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 LTQXL system using the MS/MS CID (collision-induced dissociation) mode. The method was linear in the range 0.1-1000 ng/ml(r(2) = 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 -7.2% 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 C-max 39.09 +/- 4.45 ng/mL,T-max 5.00 +/- 3.08 min, AUC(0-t) 23374 +/- 4045 min ng/mL and t(1/2) 1065 +/- 246 min.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CB - Analytická chemie, separace

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP303%2F11%2F1907" target="_blank" >GAP303/11/1907: Nové inhibitory acetylcholinesterasy odvozené od látky 7-MEOTA - potenciální léčiva pro Alzheimerovu nemoc</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chromatography. B-Analytical Technologies in the Biomedical and Life Sciences

ISSN

1570-0232

e-ISSN

—

Svazek periodika

1020

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

5

Strana od-do

85-89

Kód UT WoS článku

000374627600012

EID výsledku v databázi Scopus

—