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  • 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.

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.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (2016-04-01)
Martin Mzik, Jan Korabecny, Eugenie Nepovimova, Viktor Voříšek, Vladimir Palička, Kamil Kuca, Jana Zdarova Karasova
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 7.5 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 10 cm × 4.6 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 3 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 5 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 7.5 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 15 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 3 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 2 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm Guard Cartridge, 2.7 μm particle size, L × I.D. 5 mm × 3 mm, pkg of 3 ea
Supelco
Ascentis® Express RP-Amide, 2.7 μm Guard Cartridge, 2.7 μm particle size, L × I.D. 5 mm × 4.6 mm, pkg of 3 ea
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 3 cm × 4.6 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 7.5 cm × 4.6 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 5 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 15 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 5 cm × 4.6 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm Guard Cartridge, 2.7 μm particle size, L × I.D. 5 mm × 2.1 mm, pkg of 3 ea
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 10 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 10 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 5 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2.7 μm HPLC Column, 2.7 μm particle size, L × I.D. 15 cm × 4.6 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 10 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 3 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 7.5 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 5 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 10 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 15 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 15 cm × 3 mm
Supelco
Ascentis® Express RP-Amide, 2 μm UHPLC Column, 2 μm particle size, L × I.D. 3 cm × 2.1 mm
Supelco
Ascentis® Express RP-Amide, 2 μm Guard Cartridge, 2 μm particle size, L × I.D. 5 mm × 2.1 mm, pkg of 3 ea
Supelco
Ascentis® Express RP-Amide, 2 μm Guard Cartridge, 2 μm particle size, L × I.D. 5 mm × 3 mm, pkg of 3 ea