CKD-501 (i.e., lobeglitazone), a potent agonist for both PPARalpha/gamma, is a new
drug that has potential clinical applications in the management of type-2 diabetes.
The objective of this study was to develop a rapid and sensitive method for the determination
of CKD-501 in rat plasma and to assess the applicability of the assay to pharmacokinetic
studies. Rat plasma samples were processed using a fast flow protein precipitation
(FF-PPT) method and then introduced onto an LC-MS/MS system for quantification. The
analyte and rosiglitazone, an internal standard, were analyzed by multiple reactions
monitoring (MRM) at m/z transitions of 482.0-->258.0 for CKD-501 and 358.0-->135.0
for the internal standard. The lower limit of quantification (LLOQ) was determined
at 50 ng/mL, with an acceptable linearity in the range from 50 to 10,000 ng/mL (R>0.999).
Validation parameters such as accuracy, precision, dilution, recovery, matrix effect
and stability were found to be within the acceptance criteria of the assay validation
guidelines, indicating that the assay is applicable to estimating the concentration
in the range studied. The concentration of CKD-501 was readily quantifiable in plasma
samples up to 24 h post-dose in rats that had received an oral dose of 1 mg/kg. These
observations suggest, therefore, that the validated assay can be used in pharmacokinetic
studies of CKD-501 in small animals such as the rat.