title: Quantification of Etodolac in Human Plasma for Pharmacokinetics and Bioequivalence Studies in 27 Korean Subjects.
abstract: 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.
  
  
  
  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.
  
  
  
  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%.
  
  
  
  Thus, the new testified method was successfully applied for the pharmacokinetic and bioequivalence studies for two etodolac formulations.
authors.affiliation: Department of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul. South Korea.
authors.forename: Il-Dong
authors.initials: ID
authors.lastname: Song
authors.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.
authors.forename: Ju-Seop
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul. South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul. South Korea.
authors.forename: Se-Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul. South Korea.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul. South Korea.
authors.forename: Shin-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Global Medical Science, Sungshin Women`s University, Seoul. South Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Chun
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, Wisconsin. United States.
authors.forename: Kyu-Hyun
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D018592:Cross-Over Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D017308:Etodolac / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011897:Random Allocation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D017308:Etodolac
keywords: Bioequivalence; LC-MS/MS; NSAIDs; etodolac; internal standard; pharmacokinetics