Determination of a potential antiasthmatic compound, tibenelast, and its application to phase I clinical trials.
A sensitive and selective high-performance liquid chromatographic (HPLC) assay was developed for the determination of tibenelast, 5,6-diethoxybenzo[b]thiophene-2- carboxylic acid, in plasma and urine. The plasma assay involves protein precipitation with 4% trichloroacetic acid, while the urine assay is an automated solid-phase extraction procedure that utilizes the Waters Millilab workstation. The analysis was achieved by reversed-phase HPLC with ultraviolet detection at 313 nm. The quantitation limit of the assay was 50 ng/ml in plasma and 100 ng/ml in urine. The intra-day coefficient of variation for the plasma analysis was between 2.2 and 8.4%, while the overall inter-day coefficient of variation was 5.5 and 6.0% for the high and low calibration curves, respectively. The intra-day coefficient of variation for the urine analysis was between 0.3 and 3.0%, while the inter-day coefficient of variation was 2.1% for both the low and high validation samples. The assay methodology has been used in the evaluation of samples from pharmacokinetic and clinical safety studies.
Peyton
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Lilly Laboratory for Clinical Research, Eli Lilly and Company, Indianapolis, IN 46202.
Ziege
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D001249:Asthma / Q000188:drug therapy*; D001798:Blood Proteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D012996:Solutions; D013876:Thiophenes / Q000032:analysis* / Q000493:pharmacokinetics
D001798:Blood Proteins; D007202:Indicators and Reagents; D012996:Solutions; D013876:Thiophenes; C063779:tibenelast