Jacek Musijowski

Determination of fluoride as fluorosilane derivative using reversed‐phase HPLC with UV detection for determination of total organic fluorine

A quantitative method for fluoride determination using RP HPLC and UV detection was developed. The method is based on the reaction of fluoride with triphenylhydroxysilane in highly acidic conditions and extraction of the reaction product into n-heptane. Chromatographic conditions as well as the derivatization parameters were optimized. LOQ for fluoride ion was evaluated as 0.25 μM (4.75 ppb) and linear range of response up to 75 μM (1.42 ppm) was obtained. The method was developed as a part of a procedure designed for the determination of total organic fluorine in natural waters, using SPE on a carbon sorbent and sodium biphenyl reagent for the defluorination reaction. LOD for a model compound, perfluorooctanoic acid, calculated for the complete procedure with 2000-fold preconcentration, is 20 ppt (n=4). Initial results show feasibility of total organic fluorine determination for environmental purposes.

Preconcentration and decomposition of perfluorinated carboxylic acids on an activated charcoal cartridge with sodium biphenyl reagent and its determination at μg L−1 level on the basis of flow injection-fluorimetric detection of fluoride ion

Perfluorinated surfactants of heptafluorobutylate and pentadecafluorooctanoate ions were adsorbed on an activated charcoal cartridge and decomposed with sodium biphenyl (SBP) reagent to form inorganic fluoride ion. The fluoride ion thus formed was determined by flow injection analysis (FIA) using quercetin-Zr complex as a fluorimetric reagent, where lambda(ex) and lambda(em) were 422 and 491 nm, respectively. The limit of detection for fluoride ion by the FIA system was developed to 1.1 x 10(-6)M (signal to noise ratio of three), when 50% (v/v) tetrahydrofuran (THF) was used as a dissolving solvent for quercetin. The perfluorinated surfactants in the sample solution were quantitatively adsorbed on the cartridge containing 100mg of activated charcoal and were decomposed with 0.5 mL of sodium biphenyl reagent after drying thoroughly by flowing through dry nitrogen gas. The fluoride ion formed was recovered with 3 mL of purified water as an eluent, and it was determined by the fluorimetric flow injection system. The blank fluorescence signal accompanied during the adsorption/decomposition on the cartridge was reduced by washing the activated charcoal with acetone. The blank signal was also observed from dimethoxyethane, which was used in sodium biphenyl reagent. When 600 mL sample solution was used and 200 times enrichment was applied, the heptafluorobutylate and pentadecafluorooctanoate ions at the concentrations of 2.1 microg L(-1) were quantitatively recovered as fluoride ion, and the limit of detections for the perfluorinated surfactants were 0.3 and 0.3 microgL(-1) for the two perfluorinated surfactants, respectively (3 sigma of the blank signal).

Determination of sunitinib in human plasma using liquid chromatography coupled with mass spectrometry

An original method based on liquid chromatography with single quadrupole electrospray ionization mass spectrometry was developed for the determination of sunitinib in human plasma. The quantitation limit of the method at 0.10 ng/mL is comparable to that of tandem mass spectrometry assays. The handling of all solutions containing sunitinib was performed under low-intensity red light to avoid the isomerization of sunitinib and enable quantitation using a single peak. Liquid-liquid extraction with a mixture of n-hexane/isopropanol (90:10 v/v) allowed recoveries at the level of 70%. Measurements were performed using a Zorbax SB-C18 column (3.0 mm × 150 mm, 3.5 μm) and isocratic elution with (A) 0.1% aqueous formic acid and (B) acetonitrile/methanol (80:20 v/v) in an A/B ratio of 55:45 at 35°C. Under these conditions, sunitinib is eluted at 3.8 min in 6 min of the total run time. The linearity of the calibration curve ranges from 0.10 to 150 ng/mL. The baseline separation of sunitinib and its primary metabolite, N-des-ethyl sunitinib (SU12662), as well as sharp peak shapes, suggest a possibility of extending the applied methodology to the quantitative determination of both compounds. Isotopically labeled sunitinib was used as the internal standard. All required validation tests met the acceptance criteria and proved the methods reliability and robustness. The method may be conveniently applied to study the pharmacokinetics of sunitinib in humans.

Determination of Total Organic Fluorine (TOF) in environmental samples using flow-injection and chromatographic methods

Since the perfluorinated organic compounds have been recognized as persistent organic pollutants present in the environment, food and living organisms, new analytical methods are being developed for their determination. Many of the described earlier methods focus on determination of particular fluorinated compounds, however, the specific compounds are only a part of all organic fluorine compounds present in environmental or biological samples.

Is a deuterated internal standard appropriate for the reliable determination of olmesartan in human plasma

A right choice of the internal standard is one of the most challenging tasks during bioanalytical method development. Surprisingly, among the HPLC-MS methods for the determination of a cardiovascular drug olmesartan in plasma only structural analogues or similar compounds were used as internal standards. We have tried to answer the question whether the stable isotope labelled (deuterated) internal standard, as recommended by regulatory agencies, can be used for the reliable determination of olmesartan in human plasma. An HPLC-MS method using this standard in a simplified liquid-liquid extraction procedure led to accurate and precise results in the linearity range of 5-2500ng/mL. The method is well suited for pharmacokinetic studies following a single 40mg oral dose of olmesartan medoxomil in humans. The method was fully validated according to international guidelines and successfully applied in a bioequivalence study in humans. The use of deuterated olmesartan as the internal standard afforded a reliable tool for regulatory bioanalysis that can indirectly contribute to therapy efficacy and improve the safety of patients treated with generic medicines.