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http://dx.doi.org/10.4333/KPS.2005.35.4.265

Development and Validation of an HPLC Method for the Pharmacokinetic Study of Etodolac in Human  

Cho, Hea-Young (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University, Clinical Trial Center, Chonnam National University Hospital)
Kang, Hyun-Ah (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University, Clinical Trial Center, Chonnam National University Hospital)
Moon, Jai-Dong (Medical School, Chonnam National University)
Choi, Hoo-Kyun (College of Pharmacy, Chosun University)
Lee, Yong-Bok (Institute of Bioequivalence and Bridging Study, College of Pharmacy, Chonnam National University, Clinical Trial Center, Chonnam National University Hospital)
Publication Information
Journal of Pharmaceutical Investigation / v.35, no.4, 2005 , pp. 265-271 More about this Journal
Abstract
A rapid, selective and sensitive reversed-phase HPLC method for the determination of etodolac in human serum was developed, validated, and applied to the pharmacokinetic study of etodolac. Etodolac and internal standard, ibuprofen were extracted from human serum by liquid-liquid extraction with hexane/isopropanol (95:5, v/v) and analyzed on a Luna C18(2) column with the mobile phase of 1% aqueous acetic acid-acetonitrile (4:6, v/v). Detection wavelength of 227 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed etodolac concentration $(1\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-40\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 0.05 ${\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.00 to 110.00% for etodolac with overall precision (% C.V.) being 1.08-10.11%. The percent recovery for human serum was in the range of 76.73-115.30%. Stability studies showed that etodolac was stable during storage, or during the assay procedure in human serum. The peak area and retention time of etodolac were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of etodolac in human serum samples for the pharmacokinetic studies of orally administered Lodin XL tablet (400 mg as etodolac) at three different laboratories, demonstrating the suitability of the method.
Keywords
Etodolac; Human serum; Validation; Pharmacokinetics; HPLC;
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