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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.
- Source :
-
Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences . May2016, Vol. 1020, p85-89. 5p. - Publication Year :
- 2016
-
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 × 2.1 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 (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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15700232
- Volume :
- 1020
- Database :
- Academic Search Index
- Journal :
- Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 115070114
- Full Text :
- https://doi.org/10.1016/j.jchromb.2016.02.038