A validated LC-MS/MS method for quantitative analysis of curcumin in mouse plasma and brain tissue and its application in pharmacokinetic and brain distribution studies

Abstract

Curcumin is a well-known multitherapeutic agent widely employed in neurodegenerative disorders and cancer. A selective, fast, and sensitive method employing liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous determination of curcumin in mouse plasma and brain tissue, by using salbutamol as an internal standard. Triple quadrupole mass detection with multiple reaction monitoring (MRM) mode was used to monitor the ion transitions, m/z of 369 > 285 for curcumin, and m/z of 240 > 148 for salbutamol. The method was validated for recovery, accuracy, precision, linearity, and applicability. The lower limits of quantification (LLOQ) in both matrices were 2.5 ng/mL. The inter-day and intra-day precisions and accuracy values were within the Food and Drug Administration (FDA) acceptance criteria, for both matrixes. The method was successfully applied in pharmacokinetics and brain distribution studies of curcumin after intravenous administration of free curcumin and curcumin-loaded solid lipid nanoparticles to mice. Furthermore, the application of this method along with serial blood sampling in mice has led to significant reduction in animal use and dosage and drastic improvement in speed, throughput, and quality of pharmacokinetic parameters. (C) 2014 Elsevier B.V. All rights reserved.