title: Simultaneous determination of a new antituberculosis agent KBF-611 and its de-acetylated metabolite in mouse and rabbit plasma by HPLC.
abstract: 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 microg/mL and 0.02-1 microg/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 inter-day 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.
authors.affiliation: Biopharmacy and Pharmacokinetic Division, Department of Pharmaceutics, School of Pharmacy, Shaheed Beheshti Medical University, Tehran, Iran.
authors.forename: Farhad Mostafavi
authors.initials: FM
authors.lastname: Shahab
authors.forename: Farzad
authors.initials: F
authors.lastname: Kobarfard
authors.forename: Simin
authors.initials: S
authors.lastname: Dadashzadeh
mesh_terms: D000107:Acetylation; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D011817:Rabbits; D012015:Reference Standards; D015203:Reproducibility of Results; D013828:Thioacetazone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; C545905:KBF 611; D013828:Thioacetazone