title: Quantification of CKD-501, lobeglitazone, in rat plasma using a liquid-chromatography/tandem mass spectrometry method and its applications to pharmacokinetic studies.
abstract: 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.
authors: Research and Development Division, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
authors: Jong-Hwa
authors: JH
authors: Lee
authors: Young-Ah
authors: YA
authors: Woo
authors: In-Chang
authors: IC
authors: Hwang
authors: Choong-Yong
authors: CY
authors: Kim
authors: Dae-Duk
authors: DD
authors: Kim
authors: Chang-Koo
authors: CK
authors: Shim
authors: Suk-Jae
authors: SJ
authors: Chung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005260:Female; D047493:PPAR alpha / Q000819:agonists; D011743:Pyrimidines / Q000032:analysis* / Q000493:pharmacokinetics; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D000077154:Rosiglitazone; D053719:Tandem Mass Spectrometry / Q000379:methods*; D045162:Thiazolidinediones / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D047493:PPAR alpha; D011743:Pyrimidines; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C546215:lobeglitazone