Liquid chromatography-tandem mass spectrometric method for determination of E121 in mouse plasma and its application to pharmacokinetics. 2010

Kamal M Matar, and Ahmed Z El-Hashim, and Ivan O Edafiogho
Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait. kamal@hsc.edu.kw

A rapid LC-MS/MS method for quantification of an enaminone analog, E121 in mouse plasma using E118 as an internal standard (IS) has been developed and validated. The analyte was analyzed on C(18) column using a mobile phase of acetonitrile/methanol/ammonium acetate/formic acid (60:20:20:0.025, v/v/v/v) at a flow rate of 0.25 mL/min. Quantitation was achieved using ESI+ interface, employing MRM mode at m/z 308>262 and 222>194 for E121 and IS, respectively. The calibration standards were linear over a range of 0.10-20 microg/mL (r(2)>0.99) with an LLOQ of 0.1 microg/mL (RSD%; 11.4% and bias%; 9.5%). Intra- and inter-run precision of E121 assay ranged from 3.7 to 10.9% with accuracy (bias) that varied between -10.0 and 12.0%, demonstrating good precision and accuracy. Recoveries of E121 and the IS from plasma were above 80%. Stability of E121 in plasma showed that the analyte was stable under various conditions. The matrix effect study showed a lack of effect. The applicability of the developed method was demonstrated by measuring E121 in mouse plasma samples following intraperitoneal administration of various doses ranging from 10 to 100 mg/kg and this study demonstrates that E121 exhibits linear kinetics in the dose range studied.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D003509 Cyclohexanecarboxylic Acids Carboxylic acid derivatives of cyclohexane. Acids, Cyclohexanecarboxylic
D000814 Aniline Compounds Compounds that include the aminobenzene structure. Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem
D023421 Models, Animal Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing. Experimental Animal Models,Laboratory Animal Models,Animal Model,Animal Model, Experimental,Animal Model, Laboratory,Animal Models,Animal Models, Experimental,Animal Models, Laboratory,Experimental Animal Model,Laboratory Animal Model,Model, Animal,Model, Experimental Animal,Model, Laboratory Animal,Models, Experimental Animal,Models, Laboratory Animal

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