Determination of Posaconazole in Plasma/Serum by High-Performance Liquid Chromatography with Fluorescence Detection

Abstract

Abstract:A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of posaconazole in human plasma/serum. The method is based on a single dilution step by treating the sample with methanol, and followed by the direct injection of the sample into the HPLC system. Posaconazole and internal standard ketoconazole in the methanol extract are subsequently analyzed by using a fluorescence (FL) detector at optimized wavelengths (excitation 245 nm and emission 380 nm). The method achieves a linear detector response for peak height measurements over the concentration range of 0.1-10 µg/mL which adequately covers the therapeutic range for appropriate patient monitoring. The chromatographic time is less than 8 min per injection, an improvement over most published HPLC/FL or HPLC/UV methods. The method's limit of quantitation, linearity, imprecision, and accuracy met all criteria required by the Guidance for Industry Bioanalytical Method Validation. In comparison to other published methods, the current method would be of interest to analytical and clinical laboratories because it employs simple, rapid, and cost-effective procedures.

Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of β‐Lactam Antibiotics in Critically Ill Children

“…Within‐day and between‐day assay precision and accuracy of the quality control for all 3 drugs were satisfactory (CV < 15%). Assay data examined for analytical methods met all criteria recommended by the FDA for bioanalytical method validation including accuracy, precision, selectivity, sensitivity, reproducibility, and stability, 15 as previously described for β‐lactam antibiotics in the literature 16 and performed for other medications by our laboratory 17,18 …”

Therapeutic drug monitoring of posaconazole for effective prophylaxis of invasive fungal infections in pediatric patients: a pilot study

“…Up to now, a dozen methods for the estimation of posaconazole in biological samples have been published. High-performance liquid chromatography with UV [5][6][7][8] or FLD [9][10][11] detection and liquid chromatography-tandem mass spectrometry [12][13][14][15][16] remain the most advantageous in terms of therapeutic monitoring of drugs, because they enable reliable results to be obtained in a relatively short time.…”

“…An extremely important facet of TDM practice is the aliquot of the matrix that is required for analysis, especially in pediatric patients. When compared to previously published HPLC-UV [6][7][8] or HPLC-FLD [9][10][11] methods in which the sample volume ranges from 100 to 500 μL, the current method allows the determination of posaconazole in plasma with a smaller serum sample (50 μL) and a smaller injection volume (2 μL). Finally, the total chromatographic run time of the method used is less than 7 min, which is very important in TDM practice when results must be obtained as quickly as possible.…”

Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole

“…POS concentration was studied by the HPLC method using an Agilent Technologies 1200 system (Agilent, Waldbronn, Germany) and a Poroshell ® 120 EC-C18 2.7 µM ODS 4.6 × 150 mm, 2.7 µm column (Agilent, Waldbronn, Germany). As the mobile phase, acetonitrile: methanol: water (60:20:20, v/v) with a flow rate of 0.5 mL/min was applied [52]. The UV detection was operated with a wavelength of 240 nm.…”