Study of tamoxifen urinary metabolites in rat by ultra‐high‐performance liquid chromatography time‐of‐flight mass spectrometry

Tamoxifen (TMX) is a nonsteroidal estrogen antagonist drug used for the treatment of breast cancer. It is also included in the list of banned substances of the World Anti Doping Agency (WADA) prohibited in and out of competition. In this work, the excretion of urinary metabolites of TMX after a single therapeutic dose administration in rats has been studied using ultra‐high‐performance liquid chromatography electrospray time‐of‐flight mass spectrometry (UHPLC‐TOFMS). A systematic strategy based on the search of typical biotransformations that a xenobiotic can undergo in living organisms, based on their corresponding molecular formula modification and accurate mass shifts, was applied for the identification of TMX metabolites. Prior to UHPLC‐TOFMS analyses, a solid‐phase extraction step with polymeric cartridges was applied to urine samples. Up to 38 TMX metabolites were detected. Additional collision induced dissociation (CID) MS/MS fragmentation was performed using UHPLC‐QTOFMS. Compared with recent previous studies in human urine and plasma, new metabolites have been reported for the first time in urine. Metabolites identified in rat urine include the oxygen addition, owing to different possibilities for the hydroxylation of the rings in different positions (m/z 388.2271), the incorporation of two oxygen atoms (m/z 404.2220) (including dihydroxylated derivatives or alternatives such as epoxidation plus hydroxylation or N‐oxidation and hydroxylation), epoxide formation or hydroxylation and dehydrogenation [m/z 386.2114 (+O –H₂)], hydroxylation of the ring accompanied by N‐desmethylation (m/z 374.2115), combined hydroxylation and methoxylation (m/z 418.2377), desaturated TMX derivate (m/z 370.2165) and its N‐desmethylated derivate (m/z 356.2009), the two latter modifications not previously being reported in urine. These findings confirm the usefulness of the proposed approach based on UHPLC‐TOFMS. Copyright © 2015 John Wiley & Sons, Ltd.     

Elucidating collision induced dissociation products and reaction mechanisms of protonated uracil by coupling chemical dynamics simulations with tandem mass spectrometry experiments

In this study we have coupled mixed quantum‐classical (quantum mechanics/molecular mechanics) direct chemical dynamics simulations with electrospray ionization/tandem mass spectrometry experiments in order to achieve a deeper understanding of the fragmentation mechanisms occurring during the collision induced dissociation of gaseous protonated uracil. Using this approach, we were able to successfully characterize the fragmentation pathways corresponding to ammonia loss (m/z 96), water loss (m/z 95) and cyanic or isocyanic acid loss (m/z 70). Furthermore, we also performed experiments with isotopic labeling completing the fragmentation picture. Remarkably, fragmentation mechanisms obtained from chemical dynamics simulations are consistent with those deduced from isotopic labeling. Copyright © 2015 John Wiley & Sons, Ltd.     

Degradable poly(ester triazole)s based on renewable resources

The copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC) click polymerization has been used to obtain novel linear poly(ester triazole)s by reaction of bis‐alkyne having ester linkage and bis‐azido monomers, most of them derived from carbohydrates, such as glucose, arabinose, and erythrose, and therefore coming from natural renewable resources. The resulting polyesters had weight‐average molecular weights in the 11,500–148,000 range and were characterized by GPC, IR, and NMR spectroscopies. Thermal studies revealed them to be amorphous and stable up to 200 °C under nitrogen. Degradation studies showed that they were hydrolytically degradable. These studies were carried out at 50 °C in phosphate buffer solution at pH 7.4, and were monitored by GPC, and NMR spectroscopy. Finally, novel network hydrogels were obtained by crosslinking reaction of the poly(ester triazole) chains with hexamethylene diisocyanate. The water absorption and the kinetic parameters of the networks were studied. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2481–2493     

UV protective textiles by the deposition of functional ethylcellulose nanoparticles

Ethylcellulose (EC) nanoparticles have been widely investigated for their use as drug delivery systems. However, their application on the textile field has been hardly studied. In this work, the use of EC nanoparticles as nanocarriers of active or lipid soluble compounds and their subsequent deposition on cotton textile is proposed in order to obtain functional textiles. A UV protective textile has been obtained after deposition of EC nanoparticles loaded with a liposoluble UV filter on cotton fabrics. The EC/cotton affinity and the attachment mechanism of EC nanoparticles on cotton substrate was studied by means of thermal behaviour evaluation, estimation of adhesion work (W_A) and wash resistance tests. It is proposed that during EC nanoparticles deposition on cotton fabric, entanglement of polymeric chains is favoured, thus improving adhesion of EC nanoparticles on cotton substrate. The functionality of cotton textile was assessed by ultraviolet protection factor (UPF) measurements, showing a high UPF value (UPF = 45). Evaluation of UPF as a function of washing cycles were carried out on treated cotton fabrics. Washed fabrics still provided good UV protection (UPF ≥ 25), evidencing the presence of nanoparticles after washing cycles and the durability of the conferred functionality.     

Controlled radical copolymerization of styrene and maleic anhydride and the synthesis of novel polyolefin‐based block copolymers by reversible addition–fragmentation chain‐transfer (RAFT) polymerization

Reversible addition–fragmentation chain transfer (RAFT) was applied to the copolymerization of styrene and maleic anhydride. The product had a low polydispersity and a predetermined molar mass. Novel, well‐defined polyolefin‐based block copolymers were prepared with a macromolecular RAFT agent prepared from a commercially available polyolefin (Kraton L‐1203). The second block consisted of either polystyrene or poly(styrene‐co‐maleic anhydride). Furthermore, the colored, labile dithioester moiety in the product of the RAFT polymerizations could be removed from the polymer chain by UV irradiation. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3596–3603, 2000     

Role of polycation promoters in the cobalt(II) phthalocyaninetetracarboxylic and -octacarboxylic acid-catalyzed autoxidation of mercaptoethanol

The promoting effects of 2,4-ionene on the cobalt(II) phthalocyaninetetracarboxylic acid-[CoPc(COOH)₄] and cobalt(II) phthalocyanineoctacarboxylic acid-[CoPc(COOH)₈] cata-lyzed autoxidation of 2-mercaptoethanol were studied. Dimerization of the CoPc(COOH)₄ catalyst, combined with the disappearance of the catalytically inactive μ-peroxo complex and the appearance of substrate enrichment in the presence of 2,4-ionene, results in a 40-fold enhancement of the oxidation rate as compared with the polymer-free system. UV-VIS spectroscopy indicates that CoPc(COOH)₈ is incapable of forming μ-peroxo complexes or 2,4-ionene-induced dimeric catalyst species under normal reaction conditions. Thus, it was possible to study exclusively the ionene-induced effect of substrate enrichment. Addition of 2,4-ionene to an aqueous CoPc(COOH)₈ solution results in an activity enhancement by a factor of 2-3, which can be ascribed to substrate enrichment. Additionally, using mono-disperse ionene oligomers showed a molecular weight dependence of 2,4-ionene on the catalytic activity of CoPc(COOH)₈, as was observed for the conventional 2,4-ionene/cobalt phthalocyaninetetrasodiumsulfonate system. The optimal polycation/catalyst ratios of both systems decrease with increasing chain length of 2,4-ionene, until a constant value is reached. This leads to the conclusion that the optimal polymer/catalyst ratios are predominantly determined by substrate enrichment. © 1995 John Wiley & Sons, Inc.     

Novel conductive nanocomposites from perfluoropolyether waterborne polyurethanes and carbon nanotubes

The exceptional electrical conductivity of carbon nanotubes (CNTs) has been exploited for the preparation of conductive nanocomposites based on a large variety of insulating polymers. Among these, perfluoropolyether‐polyurethanes (PFPE‐PUs) represent a class of highly performing fluorinated materials with excellent water/oil repellency, chemical resistance, and substrate adhesion. The incorporation of highly conductive fillers to this class of highly performing materials allows them to be exploited in new technological and industrial fields where their unique properties need to be combined with the electrical conductivity or the electrostatic dissipation properties of carbon nanotubes. However, no studies have been presented so far on nanocomposites based on PFPE‐PUs and CNTs. In this work, polymer nanocomposites based on waterborne PFPE‐PUs and increasing amounts of carboxylated multiwall CNTs (COOH‐CNTs) were prepared and characterized for the first time. The effect of increasing concentration of COOH‐CNTs on the physical, mechanical, and surface properties of the nanocomposites was investigated by means of rheological measurements, dynamic mechanical analysis, thermal characterization, optical contact angle measurements, and scanning electron microscopy. In addition, electrical measurements showed that the highly insulating undoped PFPE‐PU system undergoes substantial modifications upon addition of COOH‐CNTs, leading to the formation of conductive nanocomposites with electrical conductivities as high as 1 S/cm. The results of this study demonstrate that the addition of COOH‐CNTs to PFPE‐PU systems represents a promising strategy to expand their possible use to technological applications where chemical stability, water/oil repellence and electrical conductivity are simultaneously required. Copyright © 2014 John Wiley & Sons, Ltd.     

Linear poly(amide triazole)s derived from d‐glucose

The click reaction between azides and alkynes is been increasingly employed in the preparation of polymers. In this article, we describe the synthesis and click polyaddition reaction of a new A‐B‐type amide monomer—prepared from d ‐glucose as renewable resource—containing the alkyne and azide functions. Both Cu(I)‐catalyzed and metal‐free click polymerization methods were used to prepare glucose‐derived poly(amide triazole)s. The resulting polymers had weight‐average molecular weights in the 45,000–129,000 range and were characterized by GPC, IR, and NMR spectroscopies. Thermal and X‐ray diffraction studies revealed them to be amorphous. Their qualitative solubilities in various solvents and their water sorption have been studied. The poly(amide triazole)s having the alcohol functions protected as methyl ether were water‐soluble. The presence of the amide functions along the polymer chain made these polytriazoles degradable in the presence of sodium deuteroxide. The degradation was monitored by NMR analysis, and the degradation product was characterized by HRMS. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 629–638     

Micro solid‐phase derivatization analysis of low‐molecular mass aldehydes in treated water by micellar electrokinetic chromatography

A MEKC method was developed for the determination of aliphatic and aromatic low‐molecular mass aldehydes (LMMAs) in treated water samples. The method involves the precapillary derivatization and extraction of the aldehydes on a Telos?ENV μ‐SPE column impregnated with 2,4‐dinitrophenylhydrazine . After elution of the hydrazones with ACN, the derivatives were analyzed using MEKC–DAD. Resolution of the MEKC procedure was studied by changing the pH and the concentration of the buffer, the type, and the concentration of surfactant, and the organic modifier content in the BGE. A running buffer consisting of a phosphate buffer (pH 7.2, 75 mM) with CTAB (50 mM) and ACN (30%) gave the best results. Linearity was established over the concentration range 0.5–500 μg/L and LODs from 65 to 775 ng/L; the interday precision was expressed as the RSD of the aldehydes ranging from 6.6 to 8.4%. Matrix effects were shown to be negligible by comparing the response factors obtained in ultrapure and treated waters. Aldehydes were readily determined at 1.1–8.4 μg/L levels in ozonated and chlorinated water samples, the method proposed being the first CE contribution developed for the systematic analysis of both aliphatic and aromatic LMMAs in water samples.     

Direct characterization of aqueous extract of Hibiscus sabdariffa using HPLC with diode array detection coupled to ESI and ion trap MS

The phenolic fraction and other polar compounds of the Hibiscus sabdariffa were separated and identified by HPLC with diode array detection coupled to electrospray TOF and IT tandem MS (DAD‐HPLC‐ESI‐TOF‐MS and IT‐MS). The H. sabdariffa aqueous extract was filtered and directly injected into the LC system. The analysis of the compounds was carried out by RP HPLC coupled to DAD and TOF‐MS in order to obtain molecular formula and exact mass. Posterior analyses with IT‐MS were performed and the fragmentation pattern and confirmation of the structures were achieved. The H. sabdariffa samples were successfully analyzed in positive and negative ionization modes with two optimized linear gradients. In positive mode, the two most representative anthocyanins and other compounds were identified whereas the phenolic fraction, hydroxycitric acid and its lactone were identified using the negative ionization mode.