nnd-502 and posaconazole

A new, accurate and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) as an analytical method for the quantitative determination of eight antifungal drugs in spiked human plasma has been described optimized and validated.. The analyzed compounds were voriconazole (VOR), luliconazole (LUL), clotrimazole (CLO), tioconazole (TIO), posaconazole (POS), ketoconazole (KET), sertaconazole (SER) and terconazole (TER).. The separation of the analyzed compounds was conducted using a novel pentabromobenzyl column known as COSMOSIL PBB-R (150 mm × 4.6 mm I.D., particle size 5 μm). The analysis of the studied drugs was determined within 14 min using a diode array detector and the mobile phase consisted of: 10 mM potassium dihydrogen phosphate buffer (pH 2.1): Methanol (2: 98 v/v). A linear response was observed for all compounds in the range of concentration studied. Sample preparation was done through liquid-liquid extraction using diethyl ether.. This proposed method was validated in terms of linearity, limit of quantification, limit of detection, accuracy, precision and selectivity. The method was successfully applied for the determination of these drugs in their pharmaceutical formulations and in human plasma samples.

Topics: Antifungal Agents; Chromatography, High Pressure Liquid; Clotrimazole; Humans; Hydrocarbons, Brominated; Imidazoles; Ketoconazole; Liquid-Liquid Extraction; Molecular Structure; Thiophenes; Triazoles; Voriconazole

Luliconazole is an imidazole antifungal agent used in topical form for the treatment of onychomycosis and dermatophytosis. In vitro activity of luliconazole against dermatophytes, Candida, black fungi, Fusarium and Aspergillus species have been investigated. Rhodotorula spp. are environmental yeasts and emerged as opportunistic pathogens among immunocompromised patients. Rhodotorula's human infections are usually resistant to treatment with antifungal drugs especially triazoles and echinocandins. The present study aimed at the molecular detection of environmental isolates of Rhodotorula spp. Then, antifungal efficacy of luliconazole was evaluated against isolates and compared to other routine systemic antifungals including; caspofungin, posaconazole, fluconazole, itraconazole, amphotericin B, and voriconazole. The biofilm production of Rhodotorula isolates was also evaluated. In this study, 39 isolates of Rhodotorula spp. were isolated from the environment, detected using molecular methods, and tested against luliconazole. Then, the anti-fungal activity of luliconazole compared with several routine antifungals. Also, biofilm formation by using a crystal violet staining assay was performed. Our finding showed that luliconazole has a very high minimum inhibitory concentration (MIC) value (1-8 µg/ml) against Rhodotorula spp. Besides, 100% of Rhodotorula strains were resistant to caspofungin, followed by fluconazole 94.7% and voriconazole 74.4%. Amphotericin B was demonstrated excellent in vitro activity against this genus. Our result indicated that 59% of Rhodotorula spp. were in the mid-range of biofilm production. Our results indicated that luliconazole does not effective against the genus Rhodotorula. Furthermore, amphotericin B is the best drug against this genus in comparison to caspofungin and other azole drugs.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Caspofungin; DNA, Fungal; DNA, Ribosomal Spacer; Fluconazole; Humans; Imidazoles; Itraconazole; Microbial Sensitivity Tests; Phylogeny; Rhodotorula; Species Specificity; Triazoles; Voriconazole