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KMID : 0043320090320101453
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Archives of Pharmacal Research
2009 Volume.32 No. 10 p.1453 ~ p.1460
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Simultaneous Determination of a New Antituberculosis Agent KBF-611 and its De-acetylated Metabolite in Mouse and Rabbit Plasma by HPLC
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Dadashzadeh Simin
Shahab Farhad Mostafavi
Kobarfard Farzad
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Abstract
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KBF-611 is a new thiosemicarbazone derivative which has demonstrated significant antituberculosis effect. A sensitive and specific HPLC method was established and validated for the determination of KBF-611 and its deacetylated metabolite (KM) in mouse and rabbit plasma. Chromatographic separation was achieved on a Eurospher-100 C8 column using acetonitrile, methanol, phosphate buffer (pH 7) and TEA (25:5:70:0.1, v/v), as mobile phase at a flow rate of 1 mL/min. KBF-611, KM and internal standard (4-acetamido?3?chlorobenzaldehyde thiosemicarbazone) were detected at the wavelength of 323 nm. The calibration curves were linear within the concentration range from 0.02-5 μg/mL and 0.02-1 μg/mL for KBF-611 and KM respectively. The limit of detection and the limit of quantitation were 6 ng/mL and 20 ng/mL respectively for both KBF-611 and KM. The relative standard deviation for intra- and interday precision was less than 7.5%. Average recoveries were 70.8% and 75.0% for KBF-611 and KM respectively. The established HPLC method was validated to be a simple, rapid and reliable procedure and successfully applied to study the preclinical pharmacokinetics of KBF-611 and KM in mice and rabbits.
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KEYWORD
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KBF-611, Antituberculosis, HPLC, Preclinical pharmacokinetics, Deacetylated metabolite
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