Quantitative and Qualitative Analysis of CKD-501, Lobeglitazone, in Human Plasma and Urine Using LC–MS/MS and Its Application to a Pharmacokinetic Study

Abstract

A simple, rapid and sensitive LC-MS/MS method in positive ion mode was developed and validated to determine CKD-501, lobeglitazone, in human plasma and urine using glipizide as an internal standard (IS). Lobeglitazone is a novel thiazolidinedione (TZDs)-based peroxisome proliferatoractivated receptor (PPAR) agonist, used for the management of type-2 diabetes. After mixing the IS, dissolved in acetonitrile, with a plasma or urine sample containing lobeglitazone, 10 lL of supernatant was injected into the LC-MS/MS system. Quantification was performed in the multiple reaction monitoring (MRM) mode using transition of 481.5 ? 152.2 (m/z) for lobeglitazone and 446.1 ? 321.2 (m/z) for the IS. The method showed good linearity over concentration ranges of 0.5-1,000 ng mL -1 for plasma and 0.2-250 ng mL -1 for urine (r 2 C 0.9996). The mean percent extraction recovery of lobeglitazone was 90.8 % for plasma and 87.3 % for urine, while the recoveries of the IS were greater than 86.4 % for both. The intra-day and inter-day precision of plasma ranged from 1.1 to 3.7 and 2.5 to 3.3 % (RSD), respectively, and the intra-and inter-day precision of urine ranged from 1.5 to 2.7 and 3.2 to 3.5 %, respectively. This method is simple, sensitive, and applicable for the pharmacokinetic study of lobeglitazone in human plasma. Most of the urine concentrations of lobeglitazone were below the LLOQ because the lobeglitazone is extensively metabolized.

Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for a Rat Organic Anion Transporting Polypeptide 1B2–Mediated Interaction in Hepatic Transport

“…The concentration of LB and ATV in rat plasma samples, tissue homogenates, or cell lysates was determined using an LC-MS/MS assay method as previously described (Lee et al, 2009;Kim et al, 2012) with a minor modification. Briefly, an aliquot (50 ml) of the sample was vortex mixed with an ACN solution containing glipizide (100 ng/ml, internal standard) followed by centrifugation (16,100g for 5 minutes at 4°C).…”

Liquid chromatography and liquid chromatography coupled with tandem mass spectrometry studies for the identification and characterization of degradation products of lobeglitazone

“…The affinity of LBT for PPAR-γ was discovered to be higher when compared to other PPAR γ activators, implying that a lower dose might be employed and, as a result, unfavorable cardiovascular events, a prevalent form of toxicity for TZDs PPARs, may be reduced for LBT [7][8][9]. The liquid chromatography-mass spectrometry (LC-MS) methods existing on LBT were aimed toward pharmacokinetic and metabolite studies [10][11][12].…”