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The validation and uncertainty assessment of the analytical method developed for the simultaneous determination of 25 anticancer drugs commonly handled in hospital pharmacy was reported. Selected compounds were 5-fluorouracil, cytarabine, fludarabine phosphate, ganciclovir, gemcitabine, dacarbazine, methotrexate, pemetrexed, busulfan, raltitrexed, etoposide phosphate, topotecan, ifosfamide, cyclophosphamide, irinotecan, doxorubicin, epirubicin, daunorubicin, idarubicin, vincristine, vinblastine, vinorelbine, docetaxel and paclitaxel. Accuracy and uncertainty profiles were obtained for all compounds. Quantitative performances were satisfactory in term of specificity, sensitivity, precision and accuracy. Repeatability (1.9–25.4%) and intermediate precision (2.7–29%) were determined for all target compounds. Lower limits of quantification between 1 and 25 ng/mL were obtained. Uncertainty associated to measurement of routine samples was evaluated. The multi-targeted method was specific and reliable and was successfully applied to wipe samples from hospital pharmacy chemotherapy compounding unit and to the determination of outside contamination of vials from pharmaceutical manufacturers.

Resume Cet article rapporte un cas d’hematome sous-perioste de l’aile iliaque chez une adolescente de 14 ans dans les suites d’un traumatisme a faible cinetique. La presentation clinique est impressionnante avec atteinte neurologique peripherique par compression du nerf femoral et amyotrophie quadricipitale. La prise en charge a necessite une intervention chirurgicale pour drainage de l’hematome sous-perioste. L’evolution a ete favorable a 3 mois avec recuperation quadricipitale quasi-complete et absence de deficit sensitif persistant.

The wastewater contamination of a Swiss university hospital by active pharmaceutical ingredient (API) residues was evaluated with a three months monitoring campaign at the outlet of the main building. Flow-proportional samples were collected with an automatic refrigerated sampler and analyzed for 15 API, including antibiotics, analgesics, antiepileptic and anti-inflammatory drugs, by using a validated LC-MS/MS method. The metals Gd and Pt were also analyzed using ICP-MS. Measured concentrations were compared to the predicted ones calculated after the drug average consumption data obtained from the hospital pharmacy. The hospital contribution to the total urban load was calculated according to the consumption data obtained from city pharmacies. Lastly, the environmental hazard and risk quotients (RQ) related to the hospital fraction and the total urban consumption were calculated. Median concentrations of the 15 selected compounds were ranging from 0.04 to 675 μg/L, with a mean detection frequency of 84%. The ratio between predicted and measured environmental concentrations (PEC/MEC) has shown a good accuracy for 5 out of 15 compounds, revealing over- and under-estimations of the PEC model. Mean daily loads were ranging between 0.01 and 14.2g/d, with the exception of paracetamol (109.7 g/d). The hospital contribution to the total urban loads varied from 2.1 to 100% according to the compound. While taking into account dilution and removal efficiencies in wastewater treatment plant, only the hospital fraction of the antibiotics ciprofloxacin and sulfamethoxazole showed, respectively, a high (RQ>1) and moderate (RQ>0.1) risk for the aquatic ecosystems. Nevertheless, when considering the total urban consumption, 7 compounds showed potential deleterious effects on aquatic organisms (RQ>1): gabapentin, sulfamethoxazole, ciprofloxacin, piperacillin, ibuprofen, diclofenac and mefenamic acid. In order to reduce inputs of API residues originating from hospitals various solutions can be envisioned. With results of the present study, hospital managers can start handling this important issue.

In the last decades, the number of patients receiving chemotherapy has considerably increased. Given the toxicity of cytotoxic agents to humans (not only for patients but also for healthcare professionals), the development of reliable analytical methods to analyse these compounds became necessary. From the discovery of new substances to patient administration, all pharmaceutical fields are concerned with the analysis of cytotoxic drugs. In this review, the use of methods to analyse cytotoxic agents in various matrices, such as pharmaceutical formulations and biological and environmental samples, is discussed. Thus, an overview of reported analytical methods for the determination of the most commonly used anticancer drugs is given.

A simple method based on capillary electrophoresis with a capacitively coupled contactless conductivity detector (CE-C(4)D) was developed for the determination of potassium, sodium, calcium and magnesium in parenteral nutrition formulations. A hydro-organic mixture, consisting of 100 mM Tris-acetate buffer at pH 4.5 and acetonitrile (80:20, v/v), was selected as the background electrolyte. The applied voltage was 30 kV, and sample injection was performed in hydrodynamic mode. All analyses were carried out in a fused silica capillary with an internal diameter of 50 microm and a total length of 64.5 cm. Under these conditions, complete separation between all cations was achieved in less than 4 min. The CE-C(4)D method was validated, and trueness values between 98.6% and 101.8% were obtained with repeatability and intermediate precision values of 0.4-1.3% and 0.8-1.8%, respectively. Therefore, this method was found to be appropriate for controlling potassium, sodium, calcium and magnesium in parenteral nutrition formulations and successfully applied in daily quality control at the Geneva University Hospitals.

Matrix effect on mass spectrometry response was investigated with commercially available electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) sources coupled with a single quadruple mass spectrometer. A post-column infusion system was used to observe the MS signal alterations of methadone, selected as the model compound, in plasma. For this purpose, two sample preparation procedures were tested: (1) conventional off-line sample preparations with liquid-liquid extraction (LLE), solid-phase extraction (SPE) and protein precipitation (PP) with perchloric acid (PA) and acetonitrile (ACN) and (2) on-line SPE with two different extraction columns packed with a large particle support (LPS) and with restricted access material (RAM), respectively. Whatever the sample preparation procedures, APCI source appeared to be less liable to matrix effect than ESI source. Among the different off-line sample preparations, LLE was the most efficient extraction procedure. With other techniques, MS signal was affected not only by endogenous material but also by procedure introduced compounds. Moreover, on-line SPE-LC-MS configuration exhibited matrix effects, which depend on the API source and the extraction support.

This paper presents an analysis of the influence of the active zone topology on the heat dissipation for GaAs devices. It highlights the influence of the width and the form factor on the thermal behavior of the device. It also shows the sensitivity of the thermal resistance to the increase of the dissipated power. For multi-cellular structures the impact of the thermal coupling between heat sources is studied.

We compared the effects of cholesterol feeding in male hamsters from two strains with different propensities to sucrose-induced cholelithiasis; Laboratoire de Physiologie de la Nutrition (LPN) hamsters are predisposed to developing biliary cholesterol gallstones, whereas Janvier (JAN) hamsters are not. When fed a basal control diet, LPN hamsters had a lower cholesterolemia (-21%, P = 0.01) than JAN hamsters, and a higher activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver (+148%, P = 0.018) and intestine (+281%, P < 0.0001). After feeding the same diet enriched with 0.3% cholesterol for 5 wk, cholesterolemia increased more dramatically in JAN hamsters (+235%, P < 0.001) than in LPN hamsters (+108%, P < 0.001), as did the liver concentration of cholesterol, which reached 152.30 +/- 13.00 and 44.41 +/- 9.06 micromol/g, respectively. Only JAN hamsters displayed hepatomegaly, with an increased cholesterol saturation index of the gallbladder bile (+100%, P < 0.01), due to the cholesterol challenge. In liver, cholesterol feeding reduced cholesterol 7alpha-hydroxylase activity and mRNA level, and stimulated sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase activities. Hepatic levels of LDL receptor decreased by approximately 60% in both strains, whereas HDL receptor scavenger class B type 1 (SR-BI) levels were unaffected by dietary cholesterol. The greater resistance of LPN hamsters to the hypercholesterolemic diet can be explained by a lower capacity to store cholesterol in the liver and greater efficiency in reducing the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in response to cholesterol feeding [from 11263 to 261 pmol/(min x organ) in LPN hamsters and from 4530 to 694 pmol/(min x organ) in JAN hamsters]. These results highlight the usefulness of this two-strain model, which offers some analogy with the inverse association between the predisposition to cholelithiasis and the risk of atherosclerosis in humans.

Using three-dimensional modeling of the heat flow into the substrate, and taking into account the variation of thermal conductivity with temperature, we study the sensitivity of the thermal resistance RTH to parameters such as the substrate thickness, its nature (GaAs, Si, AlN or diamond), the topology of the power source (length and width) or even the power density. Thus, we show that the transfer of active GaAs layers onto a host substrate with a higher thermal conductivity such as Si, AlN or diamond is of greater interest than the thinning of the substrate. We developed an accurate electrothermal model for the AlGaAs/GaAs heterojunction bipolar transistor (HBT) allowing prediction of the static and mainly dynamic (RF) behavior at a high signal operating mode. We show that if the HBT layers are transferred onto a diamond substrate, a 50% gain in RF power can be expected at 10 GHz. Finally, we present the technological solutions investigated for the transfer and the heteroassembly of HBT active layers on substrates better suited for thermal dissipation.

L’objectif de cette etude etait de decrire les principales comorbidites survenant chez les patients atteints de syndrome emphyseme-fibrose (SEF) et leur impact sur le pronostic. Cette etude monocentrique et retrospective a inclus 102 patients (96 hommes, âge moyen 69 ± 15 ans) ayant un SEF diagnostique entre 2006 et 2012. Les principales comorbidites et complications presentees etaient l’hypertension pulmonaire precapillaire (48 %), les infections (30,4 %), les maladies cardiovasculaires (17,7 %), les exacerbations de BPCO (15,7 %), les exacerbations aigues de fibrose (14,7 %), et les cancers bronchopulmonaires (12,8 %). L’hypertension pulmonaire etait survenue apres un delai moyen de 8 mois, et etait severe chez 51 % des patients. Quarante-six pour cent des cancers broncho-pulmonaires n’ont pas eu de confirmation histologique, en raison d’un etat respiratoire precaire, et 69 % des patients ont recu d’emblee un traitement palliatif. La mediane de survie globale a partir du diagnostic de SEF etait de 2,88 ans, avec un taux de survie a 5 ans de 35 %. En analyse univariee, les facteurs de mauvais pronostic etaient l’hypertension pulmonaire (mediane de survie de 2,59 ans versus mediane de survie non atteinte p p = 0,035). Il existait une tendance en faveur d’une mortalite superieure (a partir du diagnostic de SEF) chez les patients ayant developpe un cancer bronchopulmonaire (2,7 et 2,88 ans respectivement, p = 0,2). Les autres complications etudiees n’avaient pas d’impact sur la survie. En conclusion, l’hypertension pulmonaire precapillaire et les comorbidites cardiovasculaires sont associees a un pronostic defavorable au cours du SEF.

The reaction of some diaryl-substituted olefins [1,1-diphenylethylene (DPE), 1,1,3,3-tetraphenyl 1-butene (TPB) and 3-phenylindene (PI)] with trifluoromethanesulphonic acid has been studied in dichloromethane by means of u.v. and 1H NMR spectroscopies. All carbocations are stable at temperatures below -30°. In the case of DPE at −70°, the carbocation initially formed is dimeric but is slowly transformed into a monomeric cation. The initiation step is too fast to be studied by conventional means except for TPB where a first order rate with respect to the olefin has been observed. For DPE and TPB, when the ratio olefin/acid is high, a 33% yield in carbocations with respect to CF3SO3H is obtained for the whole range of acid concentration investigated (10−4 −1 mol 1−1). In the case of PI, the yield is 50%. 1H NMR spectra clearly show that some acid remains unreacted in the presence of olefin. The large downfield shift of unconsumed acid is consistent with the existence of complex anions CF3SO−3, (HOSO2CF3)2 and CF3SO−3, HOSO2CF3 resulting from strong hydrogen bonds between the triflate anion and its conjugate acid.