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Liquid chromatography‐tandem mass spectrometric method for determination of E121 in mouse plasma and its application to pharmacokinetics
Author(s) -
Matar Kamal M.,
ElHashim Ahmed Z.,
Edafiogho Ivan O.
Publication year - 2010
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200900800
Subject(s) - chromatography , chemistry , analyte , ammonium acetate , formic acid , calibration curve , selected reaction monitoring , pharmacokinetics , accuracy and precision , analytical chemistry (journal) , matrix (chemical analysis) , detection limit , high performance liquid chromatography , tandem mass spectrometry , mass spectrometry , medicine , statistics , mathematics
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 μg/mL ( r 2 >0.99) with an LLOQ of 0.1 μg/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.