A method based on combining inductively coupled plasma mass spectrometry (ICP-MS) with capillary electrophoresis (CE) or an ultrafiltration step was developed to study the speciation of the serum-protein adducts of a ruthenium anticancer drug under in vitro intracellular conditions. The formation of a reactive Ru species in the cell, following the metal release from the protein, is thought to play an important role in the drug's mode of action. Glutathione and ascorbic acid at their cancer cytosol concentrations were shown to be capable of altering the metal speciation in the drug adduct with holo-transferrin but not that with albumin. The appearance of the additional peaks in ICP-MS electropherograms (by recording both Ru- and Fe-specific signals) was found to be dependent on time which allowed for kinetic assessment of the evolution of novel metal species. On the contrary, after the addition of citric acid the ruthenium ion (within the appropriately complexed scaffold) remained sequestered in the adduct. This was inferred as a proof of the speciation changes taking place by a virtue of a redox mechanism rather than due to ligand-exchange transformations. The protein-bound metallodrug was further characterized by direct ICP-MS assaying so as to confirm a partial release of ruthenium induced by glutathione.

(2015) Development and evaluation of a dry powder formulation of liposomeencapsulated oseltamivir phosphate for inhalation, Drug Delivery, 22:5, 608-618, DOI: 10.3109/10717544.2013 AbstractThis study aims to develop oseltamivir phosphate (OP) liposomes as inhalation powders by spray-drying based on the single factor investigation, which was mainly composed of lactose, L-leucine and mannitol. It was found that the ratio of OP and liposomes (1:10), inlet temperature (110 C) and airflow rate (2.3 mL/min) showed optimized physical properties of OP liposomes. Deposition was evaluated after the aerosolization of powders at 600 L/h via the Aerolizer Õ into a twin-stage impinger. The concentrations of OP and oseltamivir carboxylate (OSCA) in rats plasma using LC-MS have been determined and performed via pharmacokinetic software DAS 2.0 package. The liposomal OP dry powders displayed an average particle size around 3.5 mm with fine particle fraction (FPF ¼ 35.40%). In vitro evaluation demonstrated a sustained release pattern accounting for 20% drug release compared to that of OP solution up to 90% drug release in 2 h. And the cumulative release percentage was up to 50% in 20 h. Atrioventricular fitting results indicated that all preparations were best fitted with a two-compartment model. There was a significant difference in MRT, C max and T max (p50.01) between the two groups of liposomal OP dry powders and OP solution with t-test, which indicated that the drug released slowly from liposomal OP dry powders in the lung. To sum up, dry powders formulation of liposome-encapsulated OP for inhalation was suitable for pulmonary administration, which offering the opportunity to reduce dosing frequency.

Within a certain range, increasing the powder residence time could improve the performance of Aerolizer(®) by increasing the powder-air interaction time (the main reason) and increasing the powder-device compaction (the secondary reason). Combination of high turbulence level and sufficient powder residence time could further improve the device performance.

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The purpose of this work was to develop a method for the determination of selenium speciation in tea samples. The contents of selenium in extracts as well as in original tea samples were determined by inductively coupled plasma mass spectrometry (ICP-MS). Separation of Se(IV), Se(VI) and SeMet was achieved by a Hamilton PRP-X100 anion exchange column with the mobile phase of 40 mM (NH 4 ) 2 HPO 4 (pH 6.0)，2% CH 3 OH. Dynamic reaction cell (DRC) technology was used to reduce isobaric interferences and the optimized Rpq value was 0.4, the reaction gas flow rate was 0.4 mL min -1 . The detection limits for Se(IV), SeMet and Se(VI) were 0.307 µg⋅L -1 ，0.286 µg⋅L -1 and 0.189 µg⋅L -1 , respectively, and their corresponding RSD were 1.01%, 0.953% and 0.629%, respectively. In the extracts of 95 o C water, Se(IV) was found at the retention time of 2.27 min, as well as an unknown selenium speciation at the retention time of 1.97 min. In the extracts of black tea, an unidentified peak at the retention time of 2.45 min was also observed.