LC-MS/MS determination of tideglusib, a novel GSK-3β inhibitor in mice plasma and its application to a pharmacokinetic study in mice.

A sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of tideglusib in mice plasma using warfarin as an internal standard (I.S.) as per regulatory guidelines. Sample preparation was accomplished through liquid-liquid extraction process. Chromatographic separation was performed on Atlantis dC18 column using mobile phase A (acetonitrile) and B (5mM ammonium acetate in water) in a flow-gradient mode. Elution of tideglusib and the I.S. occurred at ∼2.06 and 1.29min, respectively. The total chromatographic run time was 3.2min. A linear response function was established in the concentration range of 20.2-1008ng/mL. The intra- and inter-day accuracy and precision were in the range of 4.61-12.6 and 6.04-11.8%, respectively. This novel method has been applied to a pharmacokinetic study in mice.