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

✍ Scribed by Kamal M. Matar; Ahmed Z. El-Hashim; Ivan O. Edafiogho

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 305 KB
• Volume: 33
• Category: Article
• ISSN: 1615-9306
• DOI: 10.1002/jssc.200900800

✦ Synopsis

Abstract

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.