title: [Determination of bifonazole using HPLC in pharmacokinetic studies].
abstract: A sensitive method for HPLC quantification of bifonazole, an antimycotic drug, in the skin and plasma was developed. The skin samples were homogenized with the use of a physiological solution (1:5) and then centrifuged at 2000 r.p.m. for 20 minutes. Bifonazole was extracted from the homogenates or plasma with methylene chloride. The organic phase was evaporated to dryness under nitrogen at 45 degrees C, the residue was redissolved in methanol and an aliquot of 0.03 ml was injected to the HPLC system for determination of the drug content. A Silasorb C column (30 cm x 4.6 mm, 10 microns) was used. The mobile phase consisted of acetonitrile, 0.12 M sodium acetate and methanol (84:15:1). The flow rate was 1.5 ml/min. The UV absorption was monitored at lambda 254 nm. The calibration plots were linear within the concentration ranges of 1 to 20 micrograms/g. The determination limit was 0.02 microgram/g. The bifonazole pharmacokinetics was studied with the developed method on rats after a single application of 1 per cent drug cream to the skin. The cream was manufactured by two different companies (formulations A and B). The skin and blood samples were collected 0.5, 1, 2, 6, 24 and 48 hours after the bifonazole cream application in a dose of 1 g/kg. The plasma levels of bifonazole were below the detection limit of the method throughout the observation period whereas the skin concentrations could be measured within 0.5-48 hours. Despite the faster skin penetration of bifonazole applied as formulation A the relative extent of the penetration was close to 1 (0.95) and the mean residence times were similar (14.9 and 14.5 hours for formulations A and B respectively). The developed analytical procedure is useful in pharmacokinetic studies with bifonazole.
authors.forename: I B
authors.initials: IB
authors.lastname: Kadenatsi
authors.forename: I V
authors.initials: IV
authors.lastname: Agapitova
authors.forename: L V
authors.initials: LV
authors.lastname: Shustova
authors.forename: I
authors.initials: I
authors.lastname: Salib
authors.forename: V S
authors.initials: VS
authors.lastname: Dombrovskiĭ
authors.forename: E V
authors.initials: EV
authors.lastname: Gagaeva
authors.forename: E E
authors.initials: EE
authors.lastname: Kuleshova
authors.forename: A P
authors.initials: AP
authors.lastname: Arzamastsev
authors.forename: A A
authors.initials: AA
authors.lastname: Firsov
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D007093:Imidazoles / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; C036596:bifonazole
vernacular_title: Opredelenie bifonazola metodom VEZhKh pri farmakokineticheskikh issledovaniiakh.