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
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27030895
DOI
10.1016/j.jchromb.2016.02.038
PII: S1570-0232(16)30125-8
Knihovny.cz E-zdroje
- Klíčová slova
- 7-MEOTA, Acetylcholinesterase, Alzheimer disease, Donepezil, HPLC–MS, PC 48,
- MeSH
- Alzheimerova nemoc MeSH
- cholinesterasové inhibitory krev MeSH
- donepezil MeSH
- indany krev chemie farmakokinetika MeSH
- krysa rodu Rattus MeSH
- lineární modely MeSH
- piperidiny krev chemie farmakokinetika MeSH
- potkani Wistar MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- takrin analogy a deriváty krev chemie farmakokinetika MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 7-methoxytacrine MeSH Prohlížeč
- cholinesterasové inhibitory MeSH
- donepezil MeSH
- indany MeSH
- piperidiny MeSH
- takrin MeSH
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 × 2.1mm, 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 (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 Cmax 39.09 ± 4.45 ng/mL,Tmax 5.00 ± 3.08 min, AUC0-t 23374 ± 4045 min ng/mL and t1/2 1065 ± 246 min.
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