title: High-performance liquid chromatographic assay for the determination of novel triazole antifungal agents in tissue. Application to tissue distribution studies.
abstract: A simple and rugged reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection at 263 nm was developed and validated for the analysis of novel triazole antifungal agents SYN-2869 and its derivatives in tissues. The method involved homogenization with 0.01 M phosphate buffer (pH 7.8) for lung, brain and spleen tissues. The liver and kidneys were homogenized with acetonitrile:acetone (1:1). The plasma proteins were precipitated with ice-cold acetonitrile and supernatent was evaporated to dryness. The reconstituted samples were injected onto an HPLC system. SYN-2869 was separated from the matrix components on a symmetry C(18) column using a aqueous mobile phase of acetonitrile and water with a flow rate of 1 mL/min. A step gradient of 40-80% acetonitrile eluted SYN-2869 and the internal standard (SYN-2506). The linear range was 0.5-10 microgram/g (r(2) > 0.99). The limit of quantitation was 0.5 microgram/g. The inter-day precision and accuracy for SYN 2869 standard concentration were from 2.6 to 7.4% and from -1.56 to +3.29%, respectively. The method was applied to tissue samples collected from single intravenous administration to mice to evaluate the distribution of these novel antifungal agents to different tissues.
authors.affiliation: Division of Biopharmaceutics and Pharmacokinetics, NAEJA Pharmaceutical Inc. no. 2, 4290-91A St, Edmonton, Alberta, Canada T6E 5V2.
authors.forename: J K
authors.initials: JK
authors.lastname: Khan
authors.forename: H
authors.initials: H
authors.lastname: Montaseri
authors.forename: M
authors.initials: M
authors.lastname: Poglod
authors.forename: H Z
authors.initials: HZ
authors.lastname: Bu
authors.forename: M
authors.initials: M
authors.lastname: Daneshtalab
authors.forename: R G
authors.initials: RG
authors.lastname: Micetich
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D051379:Mice; D010879:Piperazines / Q000493:pharmacokinetics*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014230:Triazoles / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D010879:Piperazines; C118964:Syn 2869; D014230:Triazoles