Quantification of Etodolac in Human Plasma for Pharmacokinetics and Bioequivalence Studies in 27 Korean Subjects

Title:Quantification of Etodolac in Human Plasma for Pharmacokinetics and Bioequivalence Studies in 27 Korean Subjects

Volume: 10 Issue: 4

Author(s): Il-Dong Song, Ju-Seop Kang*, Hyun-Jin Kim, Se-Mi Kim, Dong-Xu Zhao, Shin-Hee Kim, Min-Young Chun and Kyu-Hyun Lee

Affiliation:

• Department of Pharmacology & Clinical Pharmacology Laboratory & Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, College of Medicine, Hanyang University, Seoul 133-791,South Korea

Keywords: Bioequivalence, etodolac, internal standard, LC-MS/MS, NSAIDs, pharmacokinetics.

Abstract: Objective: We developed a simple and validated liquid chromatography tandem mass spectrometry( LC-MS/MS) for quantification of etodolac using pioglitazone as an internal standard (IS) to assess pharmacokinetics and to appraise bioequivalence of two formulations of etodolac (reference and tested) in 27 healthy Korean subjects.

Methods: Isocratic mobile phase consisted of 10 mM ammonium formate and acetonitrile were used to separate the analytes on a Gemini C18 column. Also, analytes were analyzed by MS/MS in multiple reaction monitoring (MRM) mode using the transitions of (M+H)+ ions, m/z 288.2→ 172.3 and m/z 357.1→ 134.2 for quantification of etodolac and IS each. The standard calibration curves displayed significant linearity within the range of 0.2-30.0 μ g/mL (r2=0.9956, 1/x2 weighting) with LLOQ of 0.1 μg/mL.

Results: The retention times of etodolac and the IS were 0.77 min and 0.57 min each, indicating the high-throughput potential of the proposed method. The pharmacokinetic parameters were calculated from the plasma samples and data form the reference and test drugs were represented as follows; Area under plasma concentration-time curve (AUCt) (78.03 vs. 84.00 μgxh/mL), AUC∞ (86.67 vs. 93.92 μgxh/mL), maximal plasma concentration (Cmax) (19.49 vs. 18.94 μg/mL), time for maximal concentrations (Tmax) (2.13 vs. 2.26 h), Plasma elimination half-life (T1/2) (8.12 vs. 8.47 h), elimination rate constant (λz) (0.0853 vs. 0.0818 h-1). Pharmacokinetic parameters with 90% confidence interval fall within the bioequivalence range of 80-125%.

Conclusion: Thus, the new testified method was successfully applied for the pharmacokinetic and bioequivalence studies for two etodolac formulations.

Cite this article as:

Song Il-Dong, Kang Ju-Seop*, Kim Hyun-Jin, Kim Se-Mi, Zhao Dong-Xu, Kim Shin-Hee, Chun Min-Young and Lee Kyu-Hyun, Quantification of Etodolac in Human Plasma for Pharmacokinetics and Bioequivalence Studies in 27 Korean Subjects, Drug Metabolism Letters 2016; 10 (4) . https://dx.doi.org/10.2174/1872312811666170116151004

DOI https://dx.doi.org/10.2174/1872312811666170116151004	Print ISSN 1872-3128
Publisher Name Bentham Science Publisher	Online ISSN 1874-0758