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Introduction Compounding robots are increasingly being implemented in hospital pharmacies. In our hospital, the recent acquisition of a robot (RIVATM, ARxIUM) for intravenous cancer drug compounding obliged us to replace the previously used infusion devices. The objective of the present study was to assess and qualify the new intravenous sets prior to their use in our hospital and prior to the implementation of the compounding robot. Materials and Methods The ChemoLockTM (ICU Medical) was compared with the devices used previously for compounding (BD PhaSealTM, Becton-Dickinson) and infusion (Connect-ZTM, Codan Medical). The connection/disconnection of infusion devices to/from 50 mL infusion bags was tested with a dynamometer (Multitest-i, Mecmesin). Leakage contamination was visualized by a methylene blue assay and was quantified in simulated pump infusions with 20 mg/mL quinine sulfate ( N = 36/group); after the analytical assay had been validated, quinine was detected by UV-spectrophotometry at 280 and 330 nm. Groups were compared using chi-squared or Mann–Whitney U tests. Results The connection/disconnection test showed that although all the devices complied with the current standard, there was a statistically significant difference in the mean ± standard deviation compression force (51.5 ± 11.6 for the Connect-ZTM vs. 60.3 ± 11.7 for the ChemoLockTM; p = 0.0005). Leaks were detected in 32 (29.1%) of the 110 tests of the ChemoLockTM. The contamination rates were also significantly different: 13.9% for the BD PhaSealTM versus 75.0% for the ChemoLockTM; p Discussion/conclusion Our results showed that the new infusion device complied with current standards. However, the presence of contamination emphasizes the need for operators to use the recommended personal protective equipment. Further studies of contamination with cancer drugs are required.

Resume Objectifs Mener une intervention ergonomique en suivant la methodologie de l’analyse de l’activite du processus de formations des internes en pharmacie clinique a l’analyse des prescriptions. Methodes L’evaluation a ete realisee sur deux semestres : de mai a octobre 2016 (premiere etude) et de novembre 2016 a avril 2017 (deuxieme etude). Les entretiens et observations ont ete effectues par une ergonome experte dans ce type d’evaluation. La premiere etude reposait sur des observations du dispositif de formation et des entretiens a plusieurs temps. La deuxieme etude a permis d’accompagner les pharmaciens et d’evaluer les changements suite aux recommandations de la precedente etude. Resultats Six et neuf internes ont participe respectivement a la premiere et deuxieme etude. Au cours de la premiere etude, 6 difficultes ont ete remontees permettant la prise de decisions d’implementation et dont le suivi a ete realise au cours de la deuxieme etude. Les retours des internes etaient globalement positifs pour la formation a la prise de fonctions, mais negatif pour l’etape de qualification. Le nombre moyen de craintes exprimees par les internes etait plus eleve en debut (2,9 ± 0,9 craintes) qu’en fin de stage (1 ± 0,7 crainte). Conclusions Le dispositif de formation a ete adapte aux attentes et ressentis des internes. Les suivis en debut et tout au long du stage des internes etaient primordiaux. La prochaine etape sera d’evaluer l’apport des tableaux de bord de suivi des competences en pharmacie clinique mis en place dans le nouveau diplome d’etudes specialisees de pharmacie hospitaliere.

OBJECTIVES: The objectives were to compare clinical pharmacist interventions between two care groups: COVID-19-positive and COVID-19-negative patients, and to identify drugs that require particular attention, especially those involved in COVID-19 management. METHODS: A prospective cohort study was conducted on patients with positive and negative COVID-19 statuses admitted to Lille University Hospital over 1 month. Pharmaceutical analysis instigated interventions to rectify drug-related errors. For each pharmaceutical intervention (PI), the anatomical therapeutic chemical classification of the drug and the outcome of such an intervention were specified. RESULTS: The study included 438 patients. Prescription analysis led to 188 PIs performed on 118 patients (64 COVID-19-positive patients and 54 COVID-19-negative patients). Most drug-related problems were incorrect dosage representing 36.7% (69/188) of all interventions: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The most frequent PI in 34% (64/188) of cases was terminating a drug: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The main drug classes involved were antithrombotic agents (20.7%, 39/188), antibacterials for systemic use (13.8%, 26/188) and drugs for gastric acid-related disorders (6.4%, 12/188). Study population was limited to a single centre over 1 month. CONCLUSION: No difference in PI was noted between the two groups. The presence of pharmacists led to a reduction in drug-related prescription problems, especially for antithrombotic and antibacterial drugs for both groups. Clinical pharmacy commitment in such a pandemic is therefore important.

Phthalates and other plasticisers are extensively used in medical devices (MD) from which they can leach out and lead to potential multiple problems for the patients. This exposure is a major issue because it is associated with reproductive and neurodevelopment disorders. The Neonatal Intensive Care Units (NICU) population is at high risk due to the daily intensive medical interventions, the reduced ability of newborns to remove these contaminants and their higher sensitivity to endocrine disruptors. We conducted a multicentric biomonitoring study to assess and compare the urinary levels of DEHP (di-(2-ethylhexyl)phthalate), DEHTP (di-(2-ethylhexyl)terephthalate) and TEHTM (tri-(2-ethylhexyl)trimellitate) metabolites as biomarkers of this exposure during and after the newborns' stay in NICU. Daily urinary samples were collected in NICU and at discharge from the hospital for each patient. MD sources and exposure factors were also investigated. 508 urinary samples from 97 patients enrolled in centres 1 and 2 (C1/C2) were collected. The exposure of newborns to DEHP was greater than that of DEHTP and TEHTM, with a median concentration of DEHP metabolites (C1:195.63 ng/mL;C2:450.87 ng/mL) respectively 5 to 10 times higher and 57 to 228 times higher than the median concentrations of DEHTP and TEHTM metabolites. The urinary concentrations of DEHP and TEHTM metabolites were significantly lower at discharge than in NICU, with a 18-and 35-fold decrease for DEHP and a 4 and 8-fold decrease for TEHTM, respectively for C1 and C2, but were similar for DEHTP metabolites. MD used for respiratory assistance, infusion therapy,enteral nutrition and transfusion were the main sources of exposure. Smaller gestational age and body weight significantly increased the newborns' exposure. The elevated levels of DEHP metabolites in NICU patients are still alarming. Additional efforts are necessary to promote its substitution in MD by possibly safer alternatives such as TEHTM and DEHTP, particularly when used for the care of newborns.

Purpose Midazolam is a benzodiazepine derivative commonly used in intensive care units to control sedation. Its use requires dilution of a 5-mg/mL commercial solution to a target concentration of 1 mg/mL. A study was conducted to evaluate the stability of diluted ready-to-use 1-mg/mL midazolam solutions over 365 days when stored in cyclic olefin copolymer vials or polypropylene syringes. Methods A specific stability-indicating high-performance liquid chromatography coupled with UV detection method was developed for midazolam hydrochloride and validated for selectivity, linearity, sensitivity, precision, and accuracy. Three storage conditions were tested: –20°C ± 5°C, 5°C ± 3°C, and 25°C ± 2°C at 60% ± 5% relative humidity. Half of the vials were stored upside down to test for the absence of interaction between midazolam and the stopper. Particle contamination, sterility, and pH were assessed. Results The limit of stability was set at 90% of the initial concentration. After 1 year’s storage at –20°C and 5°C, concentrations remained superior to 90% under all storage conditions. At 25°C, stability was maintained up to day 90 in syringes (mean [SD], 92.71% [1.43%]) and to day 180 in upright and upside-down vials (92.12% [0.15%] and 91.57% [0.15%], respectively). No degradation products were apparent, no variations in pH values were detected, and containers retained their sterility and conformity with regard to any specific contamination during the study. Conclusion The evaluated 1-mg/mL midazolam solution was stable over a 1-year period when stored at a refrigerated (5°C) or frozen (–20°C) temperature in both vials and syringes; with storage at 25°C, the stability duration was lower. The preparation of ready-to-use midazolam solutions by a hospital pharmacy is compatible with clinical practice and could help to decrease risks inherent in dilution in care units.

Objectives Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes. Methods A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at −20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure. Results Stability was successfully maintained for every concentration and container tested when stored at −20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature. Conclusions Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services.

Vancomycin hydrochloride is an antibiotic belonging to the glycopeptide family and acts by inhibiting the synthesis of the peptidoglycan wall. This antibiotic is active against Gram-positive aerobic and anaerobic bacteria1 2 and is commonly used in hospitals to treat serious infections.3 4 Vancomycin has slow bactericidal time-dependent activity and can be administered by continuous or intermittent intravenous infusion. In France, administering vancomycin by continuous infusion over 24 hours is recommended.5 6 The Summary of Product Characteristics (SmPC) recommends reconstituting a 1 g vial with 20 mL of water for injection (WFI), then diluting it in 100 mL of saline solution. The amount of vancomycin to treat an adult infection is superior to 1 g and so the volume administered can be higher than 100 mL. This volume must be limited in children or in patients on water restriction, such as those suffering from hyponatraemia and cardiovascular diseases or are in intensive care.7 Some studies on vancomycin stability have already been performed. Solutions at 5 and 10 mg/mL were stable for 58 days at +4°C in 100 mL polyvinyl chloride (PVC) infusion bags with no specification with regard to protection from light.8 Vancomycin was stable at 5 mg/mL in PVC bags for 48 hours at +22°C without protection from light and for 7 days at +4°C with protection from light.9 Raverdy et al 10 examined the stability of vancomycin diluted in 5% dextrose at high concentration (83 mg/mL) and was stable for 72 hours at +37°C. However, none of these studies reflects real infusion conditions as vancomycin is usually administered at 30 mg/kg/day.11 12 In practice, clinical services infuse vancomycin into electric syringe pumps using 50 mL (for adults) or 20 mL (for children) syringes. No stability study has yet been performed for such concentrations, in 50 or 20 mL syringes, at room temperature, nor has the reconstitution procedure13 been …

Errors in injectable preparations with high-risk drugs can be fatal. This study aimed to identify the factors influencing the accuracy of high-risk injectable drug concentrations in appliances used for intensive care unit preparation practices. Norepinephrine (NE) was chosen as an example of a high-risk medication drug. The concentration (0.2 and 0.5 mg/mL), the diluent (sodium chloride 0.9% and 5% dextrose), and the container type (prefilled- and empty-infusion bag and syringe) were tested as potential variability factors. An ultraviolet spectrophotometric method was used for NE dosage. 108 NE solutions were prepared by five individuals (pharmacists or laboratory technicians) with clinical experience as well as experience in the aseptic preparation of solutions. The container type was found to be the only factor influencing the accuracy of NE concentration. NE solutions in syringes proved to be the most accurate while preparations in prefilled bags tended to underdose NE.

Many older adults take benzodiazepines and sedative-hypnotics for the treatment of sleep disorders. With a view to considering the possible discontinuation of hypnotics, the objectives of the present study were to describe bedtime habits and sleep patterns in older adults and to identify the sleep medications taken. An expert group developed a structured interview guide for assessing the patients’ bedtime habits, sleep patterns, and medications. During an internship in a community pharmacy, 103 sixth-year pharmacy students conducted around 10 interviews each with older adults (aged 65 or over) complaining of sleep disorders and taking at least one of the following medications: benzodiazepines, benzodiazepine derivatives (“Z-drugs”), antihistamines, and melatonin. A prospective, observational study was carried out from 4 January to 30 June 2016. The pharmacy students performed 960 interviews (with 330 men and 630 women; mean ± standard deviation age: 75.1 ± 8.8). The most commonly taken hypnotics were the Z-drugs zolpidem (n = 465, 48%) and zopiclone (n = 259, 27%). The vast majority of patients (n = 768, 80%) had only ever taken a single hypnotic medication. The median [interquartile range] prescription duration was 120 (48–180) months. About 75% (n = 696) of the patients had at least 1 poor sleep habit, and over 41% (n = 374) had 2 or more poor sleep habits. A total of 742 of the patients (77%) reported getting up at night—mainly due to nycturia (n = 481, 51%). Further, 330 of the patients (35%) stated that they were keen to discontinue their medication, of which 96 (29%) authorized the pharmacist to contact their family physician and discuss discontinuation. In France, pharmacy students and supervising community pharmacists can identify problems related to sleep disorders by asking simple questions about the patient’s sleep patterns. Together with family physicians, community pharmacists can encourage patients to discuss their hypnotic medications.

Background Vancomycin is commonly used as part of empiric antibiotic therapy in the preterm infants who develop signs and symptoms of infection. Although skin necrosis has been noted to occur following injection of vancomycin into a peripheral vein in an adult patient, this complication has not been previously described in a preterm infant. Case presentation We report the case of a very low birthweight male infant born at 30 weeks gestational age who developed skin necrosis, most likely as a complication of vancomycin administration via a peripheral venous catheter. The immature skin and endothelial cells of this preterm infant may have increased the risk of drugs related venous and skin toxicity. In this case, assumption of a cumulative toxicity with other drugs administered concomitantly via the same catheter can’t be excluded. Conclusions To prevent the risk of skin damage, we advocate that in newborn infants, the administration of vancomycin should be limited to a concentration of

Skin necrosis caused by the administration of vancomycin via a peripheral venous catheter is rarely diagnosed. We report a case of a male infant born at 30 weeks’ gestational age who developed a skin necrosis, most probably related to vancomycin administration on a peripheral venous catheter. The frailty of this critically ill newborn probably increased its risk of exposition to adverse events. To prevent any damaging effect, the administration of vancomycin at a concentration lower than 2.5 mg/mL should be recommended when a central venous catheter is not available for the administration of injectable vancomycin in critically ill newborn.

At admission, unintentional medication discrepancies (UMDs) can occur and may led to severe adverse events. Some of them are preventable through medication reconciliation (MR). As MR is a time-consuming activity, a better identification of high-risk patients of UMDs is mandatory. The objective was to identify risk factors associated with UMDs at admission in an internal medicine department. This prospective observational study was conducted from April 2017 to June 2019. At admission, inpatients had MR to obtain a complete list of home medications. This list was compared to prescriptions made at admission. All discrepancies were classified as intentional or UMDs. Univariate and multivariate analyses to identify the risk factors associated with UMDs were performed. MR was performed on 1157 patients (70.1 ± 16.8 years old); 550 MR (47.5%) contained at least one UMD. More than half of the UMDs (n = 892, 65.6%) corresponded to drug omission. The univariate analysis showed that age (> 60 years old), “living at home”, medication preparation not performed by patient, medication-intake difficulties, number of sources consulted, MR duration, presence of a high-risk drug and the number of home medications were associated with UMDs. In the multivariate analysis, adjusted on the number of sources consulted, independent risk factors were “living at home” and the number of home medications. At admission to an internal medicine department, UMDs were frequent and associated with “living at home” and poly-medication. Our findings might help physicians to identify high-risk patients of UMDs since their admission.

Interactions between medical device material and the drug itself have been evoked for polyurethane and may lead to underdosing. Polyurethane, sterilization mode, and the crosslinking level of the polymer have an influence on sorption. The aim here is to evaluate the impact of polyurethane conservation time and conditions as well as sterilization mode. Two polyurethane extension tubes were tested, one sterilized by ethylene oxide and the second by gamma radiation. Forced degradation experiments were performed. After 3 and 6 months of incubation, thermal properties, diazepam delivery and cytotoxicity of leachates were assessed. Diazepam delivery differs significantly according to the version of polyurethane. Sterilization however has no impact on diazepam delivery. No cytotoxicity was observed whatever the infusion tube and the aging conditions. In conclusion, sterilization procedures do not induce polyurethane degradation, but high temperature/relative humidity/time storage conditions lead to a slight degradation in polyurethane.

International audience; The large number of drugs administered simultaneously to neonates and children in hospital results in the formation of particles that are potentially infused. We have investigated the ability of IV in-line filters to eliminate particulate matter from multidrug infusion lines and so prevent contamination. The impact on particle occurrence of the internal volume of the IV line below the in-line filter was then evaluated. The multidrug therapy given to children was reproduced with and without in-line filtration. Three combinations with a filter were tested to vary the internal volume (V) between the filter and the catheter egress. The catheter was then connected to a dynamic particle count to evaluate the particulate matter potentially administered to children during infusion. The introduction of in-line filters led to a significant reduction in overall particulate matter, from 416,974 [208,479-880,229] to 7,551 [1,985-11,287] particles (p

Insulin aspart (Novorapid) is a rapid-acting insulin analog that is maintained in hexameric form by phenolic preservatives (phenol and metacresol) and stabilized by insulin-zinc complex. According to the manufacturers, insulin can be independently diluted either in 5% dextrose solution (D5%) or 0.9% sodium chloride solution. In reality, in most clinical units, such as the neonatal intensive care unit (NICU), insulin aspart is more frequently diluted in D5% than in saline solution due to sodium restriction. However, injectable dextrose solutions contain glucose degradation products (1) that are capable of binding proteins—like insulin—through a glycation phenomenon. Therefore, dilution of Novorapid in D5% would be more likely to cause glycated insulin and may raise a worrisome problem in terms of insulin stability. The objective of this study was to investigate the stability of insulin aspart diluted in D5% at both adult and neonate therapeutic concentrations in order to ensure its appropriateness in the preparation of insulin aspart. To address this issue, insulin aspart diluted in D5% was assayed by a stability-indicating method using high-performance liquid chromatography (HPLC) coupled with an ultraviolet (UV) detector. The nature of the formed product was determined by HPLC coupled with a mass spectrometer. The effect of …

International audience; DiEthylHexylPhthalate (DEHP) can leach out of plasticized PVC medical devices (MD) and may enter into contact with patients. This phthalate is known for its reprotoxic and endocrine disrupting effects. Its use in medical devices (MD) has been restricted and alternative plasticizers have been developed. Nevertheless, no published clinical studies exist concerning patient exposure to these alternative plasticizers during medical care. This is particularly worrisome when high-risk populations, such as newborns, are exposed to these new plasticizers in intensive care units. Our study aimed to develop a novel sensitive and selective method to simultaneously identify and quantify DEHP and 17 other plasticizer metabolites (free or glucuronide conjugates), which are specific biomarkers of DEHTP, TOTM, DINP, DINCH and DEHA exposure in human urine. This robust method uses turbulent-flow online extraction technology coupled to high performance liquid chromatography – tandem mass spectrometry. Special care was taken to address two major problems in plasticizer analysis: contamination and chromatographic separation of interfering analogue structures. The validation was assessed in synthetic urine and the linearity of response was demonstrated for all compounds (R2 > 0.99), with limits of quantification from 0.01 to 0.1 ng/ml. Accuracies ranged from 86% to 117% and inter- and intra-day precisions were

Background In hospital, medications for infusion are mostly diluted in saline. In neonatal resuscitation, glycaemic instabilities are frequently observed in premature newborns, hence insulin treatment is started. In our establishment, insulin aspart is used and diluted in a 5% dextrose solution (D5%), due to sodium restrictions in newborns. Purpose To evaluate the impact of the choice of D5% diluent on the stability of the insulin aspart at 1 U/mL. Material and methods The pharmaceutical specialty composed of insulin aspart and its two preservatives (phenol and metacresol) were diluted in saline or D5%. The impact of the diluent on the stability of insulin aspart was studied by high-performance liquid chromatography with UV detection (HPLC-UV). A stability indicator method,1 adapted from the method of Poulsen et al.2 and developed for insulin aspart diluted in saline, was used. The prospective formation of a new compound in the different diluents was evaluated by HPLC with a mass spectrometry detection (HPLC-MS) in full-scan mode. The kinetic of the new compound’s appearance was studied by relative evaluation of HPLC-UV signals during 1 week for insulin at 1 U/mL diluted in D5% (n=4). Results The three products contained in the pharmaceutical specialty diluted in saline correspond to the three signals identified in HPLC-UV (elution order: phenol, metacresol and insulin aspart). After dilution of insulin aspart in D5%, we noted a fourth signal. pH influence and forced degradation tests failed to attribute this signal to insulin or preservatives’ degradation. HPLC-MS analysis revealed a mass difference of 162 daltons between insulin and this product, which corresponds to a glycation phenomenon of insulin aspart. Finally, the kinetics shows that the insulin glycation phenomenon seems to increase with the contact time between insulin and glucose until a plateau is reached after 24 hour of contact. Conclusion This work highlighted the instability of insulin in D5% and showed the phenomenon of insulin aspart glycation. To better characterise this phenomenon, the biological effect of glycation on insulin activity have to be determined, since a decrease in activity has been observed for human insulin. References and/or acknowledgements 1. Methodological guidelines for stability studies of hospital pharmaceutical preparations. https://www.gerpac.eu/IMG/pdf/guide_stabilite_anglais.pdf 2. Poulsen, et al. Pharmal Res2008. No conflict of interest.

International audience; A wide variety of medical devices (MDs) used in hospitals are made of flexible plasticized polyvinylchloride (PVC). Different plasticizers are present in variable amounts in the PVC matrix of the devices and can leach out into the infused solutions and may enter into contact with the patients. The ARMED1 project aims to assess the migration of these plasticizers from medical devices and therefore the level of exposure in patients. For the first task of the project, eight methods were developed to directly detect and quantify the plasticizers in the PVC matrix of the MDs. We compared the overall performances of the analytical methods using standardized and validated criteria in order to provide the scientific community with the guidance and the technical specifications of each method for the intended application. We have shown that routine rapid screening could be performed directly on the MDs using the FTIR technique, with cost-effective analyses. LC techniques may also be used, but with limits and only with individual quantification of the main plasticizers expected in the PVC matrix. GC techniques, especially GC–MS, are both more specific and more sensitive than other techniques. NMR is a robust and specific technique to precisely discriminate all plasticizers in a MD but is limited by its cost and its low ability to detect and quantify plasticizer contamination, e.g. by DEHP. All these results have been confirmed by a real test, called the " blind test " carried out on 10 MD samples.

Introduction Drug incompatibilities are a constant problem in hospital care units. The multiplication of drugs injected simultaneously during patient therapy increases the risk of incompatibilities and can have a significant clinical impact. The purpose of this research was to characterize and analyze various parameters inducing variability in particle counting using a dynamic particle counter. Materials and methods Observations were performed on two-ports manifolds with two incompatible drugs, thus creating a quantifiable particulate charge. We analyzed the number of different-sized particles measured during the experiment as well as their cumulative distribution. The parameters studied on particle count were: position of the infusion device, environmental vibrations and total flow rate. Results Significantly higher particle counts were observed when the infusion device was in a vertical position or disturbed by vibrations. Total flow rate significantly reduced the number of particles. Conclusion This study enabled us to identify several variation factors through dynamic particle counting. These factors should be taken into account to reduce variability in results.

The administration of several intravenous products on the same catheter is a very common situation in neonatology, where the stakes are high and the dangers sometimes unknown to clinicians. A large number of factors are involved in this administration, directly related to the installation of the infusion line. Moreover, the therapeutics used are often limited, and excluding classic “Marketing Authorization”. Some of these products may prove to be incompatible and thus lose their effectiveness, or even generate particles that are likely to be administered to the patient. We must be aware of these risks in order to optimize the prescription and administration of these intravenous products, especially as we treat fragile and immature patients. The aim of this work is to review the literature on the subject for the prescribers of neonatology units.

International audience; To meet new regulations, alternative plasticizers to di(2-ethylhexyl) phthalate (DEHP) are now commonly used in the manufacturing of medical devices. These are: acetyl tri-n-butyl citrate (ATBC), bis (2-ethylhexyl)adipate (DEHA), dioctyl terephtalate (DEHT), di-isononylphtalate (DINP), diisononylcyclohexane-1.2-dicarboxylate (DINCH) and trioctyltrimellilate (TOTM). An HPLC-UV analysis was previously developed to characterize four of them. However, two compounds were systematically co-eluated: DEHP with DEHA and DEHT with DINP. The first derivative of UV spectra and photodiode array detection allow the quantification of DEHA and DINP. Moreover, for each plasticizer, maximum wavelength absorbance was chosen to be as specific as possible. Quantification ranged from 0.3 to 750 µg/mL according to the plasticizer. The assays were validated by analysis of variance. Our method was validated by determining the following parameters: specificity, linearity, limits of detection and quantification. The relative biases were inferior to 5% for ATBC, DEHP, DEHA and DINCH and inferior to 10% for DEHT, DINP and TOTM. Plasticizers were extracted with tetrahydrofuran and methanol. The developed method was then used to determine the composition of plasticizers in several medical devices used in clinical service. The major plasticizers were quantified from 19% to 40% w/w, traces of DEHT were found in six medical devices and DEHP in five.

Medical devices are generally made of polyvinyl chloride plasticized by six authorized plasticizers as alternatives to di-(2-ethylhexyl)-phthalate (DEHP) classified as reprotoxic class 1b. These are acetyl tri-n-butyl citrate (ATBC), di-(2-ethylhexy) adipate (DEHA), di-(2-ethylhexyl) terephthalate (DEHT), di-isononyl cyclohexane-1,2-dicarboxylate (DINCH), di-isononyl phthalate (DINP), and tri-octyl trimellitate (TOTM). The main objective of this study was to propose a new method using

Introduction La vancomycine est indiquee dans les meningites a pneumocoques en administration en continu sur 24 h pour augmenter les penetrations meningees et cerebromeningees. Pour le traitement des meningites, les posologies recommandees sont de 60 mg/kg/j en pediatrie [1] et de 35 a 45 mg/kg/j chez l’adulte [2] . Les seules donnees de stabilites sont a 10 mg/mL [3] . L’objectif est d’etudier la stabilite de la vancomycine a 83,3 mg/mL (4 g dans une seringue de 48 mL) et a 41,7 mg/mL (2 g dans une seringue de 48 mL) lors d’une perfusion continue de 24 h. Materiels et methodes Pour la vancomycine (Sandoz, France) a 83,3 mg/mL : 4 flacons de 1 g sont dilues chacun dans 12 mL de serum sale isotonique (SSI) (n = 3). Pour la vancomycine a 41,7 mg/mL : 2 flacons de 1 g de vancomycine sont reconstitues chacun par 20 mL de SSI et dilues par 10 mL de SSI (n = 3). Ces solutions sont perfusees a 2 mL/h via des prolongateurs en polyethylene (L = 150 cm, diametre interne = 1 mm) (Vygon, France) pendant 24 h a 18 °C. Les solutions sont dosees par une methode indicatrice de stabilite apres degradation forcee selon les recommandations SFPC-GERPAC [4] en chromatographie liquide-UV [5] . Les resultats sont exprimes en % de la concentration mesuree aux differents temps par rapport a la concentration initiale dans la seringue. Les solutions sont considerees comme stables si la concentration reste superieure a 90 % de la concentration initiale. La stabilite microbiologique (Pharmacopee europeenne 2.6.1) et un comptage particulaire (APSS-2000, Particle Measuring Systems, Pharmacopee europeenne 2.6.19) ont ete realises en debut de perfusion. Resultats Pour la vancomycine a 83,3 mg/mL, les concentrations sont inferieures a 90 % a partir de 12 h de perfusion. Pour la vancomycine a 41,7 mg/mL, les concentrations sont superieures a 90 % pendant les 24 h de perfusion. Le nombre de particules de plus de 10 μm de diametre est superieur au seuil tolere (6000 particules) dans les solutions a 83,3 mg/mL (12 347 ± 137 particules), et inferieur pour les solutions a 41,7 mg/mL (4708 ± 143 particules). Les echantillons sont stables microbiologiquement. Conclusion Les solutions de vancomycine a 83,3 mg/mL ne sont pas stables et ne sont pas compatibles avec une perfusion de 24 h et ne doivent pas etre administrees aux patients compte tenu de leur charge particulaire. Dans le cadre du traitement des meningites, nous preconisons la dilution de 2 g de vancomycine maximum dans une seringue de 48 mL de SSI a perfuser sur 12 h, et realiser un changement de seringue toutes les 12 h ou toutes les 8 h selon la posologie prescrite.