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KMID : 0369820050350060423
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Jorunal of Korean Pharmaceutical Sciences
2005 Volume.35 No. 6 p.423 ~ p.429
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Development and Validation of an HPLC Method for the Pharmacokinetic Study of Fenoprofen in Human
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조혜영/Cho HY
강현아/김윤균/사홍기/이용복/Kang HA/Kim YG/Sah HK/Lee YB
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Abstract
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A selective and sensitive reversed-phase HPLC method for the determination of fenoprofen in human serum was developed, validated, and applied to the pharmacokinetic study of fenoprofen calcium. Fenoprofen and internal standard, ketoprofen, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Luna C18(2) column with the mobile phase of acetonitrile-3 mM potassium dihydrogen phosphate (32:68, v/v, adjusted to pH 6.6 with phosphoric acid). Detection wavelength of 272 nm and flow rate of 0.25 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 33 factorial design using a fixed fenoprofen concentration (2μg/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?100μg/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 0.05μg/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.27 to 109.20% for fenoprofen with overall precision (% C.V.) being 5.51-11.71 %. The relative mean recovery of fenoprofen for human serum was 81.7%. Stability (freeze-thaw, short and long-term) studies showed that fenoprofen was not stable during storage. But, extracted serum sample and stock solution were allowed to stand at ambient temperature for 12 hr prior to injection without affecting the quantification. The peak area and retention time of fenoprofen 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 fenoprofen in human serum samples for the pharmacokinetic studies of orally administered Fenopron tablet (600 mg as fenoprofen) at three different laboratories, demonstrating the suitability of the method.
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KEYWORD
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Fenoprofen calcium, Human serum, Validation, Pharmacokinetics, HPLC
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