Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation

A reversed-phase high-performance liquid chromatography (rp-HPLC) system interfaced with an electrospray ionization (ESI) source coupled to tandem mass spectrometry (MS/MS) was developed and validated for the determination of cyclophosphamide (CP), ifosfamide (IF), daunorubicin (DNR), doxorubicin (DXR), and epirubicin (EPI) in human urine. The analysis of samples containing multiple analytes with a dissimilar range of polarities was carried out using a conventional reversed-phase chromatographic BDS Hypersil C8 column. The analytical run was 15 min. The triple quadrupole mass spectrometer was operated in positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 0.2 to 4.0 microg.L(-1) for CP, IF, DXR, EPI and 0.15-2.0 microg.L(-1) for DNR in human urine. The lower limit of quantification (LLOQ) was 0.2 microg.L(-1) for CP, IF, EPI and was set at 0.3 and 0.15 microg.L(-1) for DXR and DNR, respectively. The relative standard deviations (RSD%) were <11.2% for inter- and intra-day precisions. The overall accuracy was also within 114.7% for all analytes at the concentrations of the quality control samples. The potential of ionization suppression resulting from the endogenous biological material on the rp-HPLC/MS/MS method was evaluated and measured. The feasibility of the proposed HPLC/ESI-MS/MS procedure was demonstrated by analyzing urine samples from pharmacy technicians and nurses working in hospitals or personnel employed in drug-manufacturing plants.     

Chemical constituents of the essential oils of Sideritis scardica Griseb. and Sideritis raeseri Boiss and Heldr. from Bulgaria and Macedonia

The essential oils of two species of Sideritis growing spontaneously in Bulgaria and Macedonia are reported, Sideritis scardica and Sideritis raeseri. The oils of S. scardica from different locations differed significantly: in the Macedonian sample alpha-cadinol (20%) predominated, while in the oil of Bulgarian samples the main components were diterpenic compounds and octadecenol (over 20%). This is the first report of ditrpenoids in essential oil of S. scardica. The oil of S. raeseri demonstrated a distinct chemical profile with its high concentration of sesquiterpenes, main components being germacrone (25%) and elemol acetate (15.9%). The observed qualitative variability of the oil composition of S. scardica of different geographic origin could be a result of different ecologic conditions but might also reflect the well-known tendency of some Sideritis species to hybridize.     

Di- and tri-organotin(IV) complexes of the new bis(1-methyl-1H-imidazol-2-ylthio)acetate ligand and the decarboxylated analogues

The new sodium bis(1-methyl-1H-imidazol-2-ylthio)acetate, Na[(S-tim)₂CHCO₂], has been prepared in ethanol solution using 2-mercapto-1-methylimidazole, dibromoacetic acid and NaOH. New di- and tri-organotin(IV) derivatives have been synthesized from reaction between SnR_nCl_4−n (R = Ph, Cy and ⁿBu, n = 2-3) acceptors and Na[(S-tim)₂CHCO₂]. Complexes of the type {[κ¹O-(S-tim)₂CHCO₂]SnR₃} and related decarboxylated species {[κ²N,N-(S-tim)₂CH₂]SnR₂Cl₂} have been obtained and characterized by elemental analyses, FT-IR, ESIMS and multinuclear (¹H, ¹³C and ¹¹⁹Sn) NMR spectral data. The adduct {κ¹O-[(S-tim)₂CHCO₂]Sn(H₂O)(C₄H₉)₃} was characterized by single crystal X-ray studies. The dichloromethane reaction solution of {κ¹O-[(S-tim)₂CHCO₂]Sn(C₆H₅)₃} was re-crystallized and the decarboxylated species {[(S-tim)₂CH₂]SnCl(H₂O)(C₆H₅)₃} was obtained as a crystalline solid and characterized by X-ray crystallography.     

Oligothiophene-functionalized CdSe nanocrystals: preparation and electrochemical properties

The preparation of new molecular hybrids consisting of CdSe semiconductor nanocrystals, surface-functionalized with conductive and electrochemically active oligothiophene ligands, is described. Specially synthesized aniline-terminated oligoalkylthiophenes containing one, two, or four thiophene units were used for the grafting on CdSe nanocrystals, previously surface-functionalized with 4-formyldithiobenzoate. The electrochemical activity of both the inorganic and the organic parts of the hybrid was investigated by cyclic voltammetry. The oxidative doping of the organic part of the hybrid is irreversible, contrary to the case of the “free” non-grafted ligand which shows reversible doping. Furthermore, the electrochemical doping of the surface ligands, occurring at lower potentials than the oxidation of the nanocrystals, perturbs the latter process via charging of the ligands followed by slow relaxation processes. The first two authors contributed equally to this work Correspondence: Peter Reiss, Adam Pron, DSM/DRFMC/SPrAM (UMR 5819 CEA-CNRS-Université Joseph Fourier 1)/LEMOH CEA Grenoble, 17 rue des Martyrs, F-38054 Grenoble Cedex 9, France     

The use of commercially available personal UV-meters does cause less safe tanning habits: a randomized-controlled trial

UV Index information is currently recommended as a vehicle to raise public awareness about the risk of sun-exposure. It remains unknown to what extent this information can change personal sun-protective behavior. The aim of the study was to analyze the effects of UV-Index (UV-I) information provided by low cost, commercially available UV-I sensors on major indicators of sun-tanning behavior. A randomized-controlled trial was carried out on 94 healthy volunteers aged 21-23 years. After the exclusion of subjects with photosensitive disorders (n=3), 91 subjects were randomized in two arms after stratification based on phototype and sex. Both arms received a diary to be filled every day with a log of intentional sun-exposure during summer. Subjects in the intervention group also received a commercially available UV-I sensor. The UV-I sensors were switched on and the UV-value was recorded in 77% of days with sun-exposure. During days of sun-exposure, subjects randomized to the intervention group had longer average time of sun-exposure (227.7 vs 208.7 min per day, P=0.003), also between noon and 4 pm (P<0.001), and less frequently adopted sun protective measures than controls (hat [6.4%vs 10.2%, P=0.007], sunglasses [23.9%vs 30.8%, P=0.003], sunscreen [41.4%vs 47.2%, P=0.02]) and they experienced more frequent sunburns (27.8%vs 21.5%, P=0.004). The odd ratio of sunburns was 1.60 for subjects in the intervention group compared with controls (after adjustment for sex, sunscreen use and skin type). The mean UV-I value recorded by volunteers was lower (5.6 [SD+/-0.9]) than that (7.3 [SD+/-0.46]) recorded by a professional instrument in the same period at the same latitude. Poststudy laboratory tests showed that the sensor was able to detect only about 60% of the solar diffuse radiation. The use of UV-I sensors changed the sun protective behavior of sunbathers in the direction of less use of sun protective measures. One possible explanation is that the low cost UV-meters may have functioned incorrectly and under-reported UV exposure. This may have led to an underestimation of UV-I values, erroneously reassuring subjects and causing a less protective sunbathing behavior. Another hypothesis relies on a cognitive pitfall in the subjects' dealing with intermediate UV-I values, as they may have been discouraged in the use of sunscreen as they did not feel that they had yet been exposed to very harmful UV radiation.     

Membrane emulsification using membranes of regular pore spacing: Droplet size and uniformity in the presence of surface shear

During membrane emulsification it is shown that the size of the drops formed at the membrane surface may increase with increasing dispersed phase injection rate through the membrane, or it may decrease, depending on the prevailing conditions. This is illustrated using a paddle stirrer positioned above flat disc membranes with regular arrays of pores of 20 μm diameter and spacing between the pores of 80 and 200 μm. In the former case an additional mechanism for drop detachment is the push-off force, which is determined by the geometry of the drops as they deform at the membrane surface. When dispersing sunflower oil in to aqueous solutions containing Tween 20, drop sizes between 60 and 200 μm were produced, and in the case of the membrane when the push-off force was working the Coefficient of Variation of the drops formed was below 10%. The push-off force may be added to the shear-drag force to predict drop detachment. For the 200 μm pore spaced membrane this force is much less prominent than the 80 μm spaced membrane. The capillary-shear model has been modified to include this push-off force. The experimental study required the use of very low dispersed phase injection rates as well as very high rates. Hence, two different types of pumps were used to provide these: a peristaltic and syringe pumps. A small study comparing the drop size, and size distributions, showed that the pump type did not influence the drops produced by the membrane emulsification process.     

Factorization Properties in d-Dimensional Spin Glasses. Rigorous Results and Some Perspectives

In this paper we show that d-dimensional Gaussian spin glass models are strongly stochastically stable, fulfill the Ghirlanda-Guerra identities in distribution and the ultrametricity property.     

Phosphinates and layered silicates in charring polymers: The flame retardancy action in polyurethane foams

Nanocomposites of a charring polymer (like polyurethane foam) filled with aluminum phosphinate (AlPi) with or without melamine cyanurate (MelCy) have been prepared by microwave processing and their thermal stability and fire behavior have been studied. Results on the interaction between flame retardants and layered silicates were provided as well as detailed investigation of the char strength, which has been carried out using a suitably developed method based on dynamic-mechanic analysis.