分析および生物分析技術ジャーナル

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Determination of Cremophor EL in Rat Plasma by LC-MS/MS: Application to a Pharmacokinetic Study

Vijaya Bhaskar V, Anil Middha, Sudhir Tiwari and Savithiri Shivakumar

A rapid sensitive, and selective pseudo MRM based method for the determination of Cremophor EL (CrEL) in rat plasma was developed using Liquid chromatography/Tandem mass spectrometry (LC-MS/MS). The analytes were detected using atmospheric pressure chemical ionization (APCI) tandem mass spectrometry. Plasma concentrations of CrEL were quantified after administration through oral and intravenous routes in male sprague dawley rats at a dose of 0.26 g/kg. The standard curve was linear (0.9982) over the concentration range of 2.10 to 2100.00 μg/mL. The lower limit of quantitation for CrEL was 2.10 μg/mL using 50 μL plasma. The coefficient of variation and relative error for inter and intra assay at three QC levels were 1.23 to 8.87 and -12.08 to 4.10 respectively. CrEL has poor oral bioavailability with mean absolute bioavailability of 2.32%. CrEL plasma concentration profiles after oral and intravenous dosing were without spiky concentration levels. Spiky plasma concentration profiles for new chemical entities (NCEs) are a common phenomenon in drug discovery, which could be due to entrohepatic circulation, sample handling errors. A novel proposal was conveyed to the scientific community, where formulation vehicle can be analysed as qualifier in the analysis of NCEs to address the spiky profiles.