Evaluation of cancer drug infusion devices prior to the implementation of a compounding robot.

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 < 0.0001). 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.

Limitation of the migration of plasticizers from medical devices through treatment with low-pressure cold plasma, polydopamine coating, and annealing.

Poly(vinyl chloride) (PVC) is widely used in the manufacture of medical devices. The plasticizers added to PVC are potentially toxic for humans, likely to migrate, and thus unintentionally administered to patients. The objective of the present study was to reduce the migration of plasticizer (1,2-cyclohexanedicarboxylic acid, diisononylester (DINCH) or trioctyltrimellitate (TOTM)) from PVC by implementing a three-step surface treatment process: (i) pretreatment with low-pressure argon cold plasma, (ii) polydopamine coating, and (iii) post-treatment with cold plasma exposure or thermal treatment at 140 °C. Samples were then characterized in terms of the water contact angle (WCA) and the aspect in scanning electron microscopy. Plasticizer migration (n = 5) was measured using an HPLC technique with ultraviolet detection and found to depend on the treatment and the plasticizer. Plasticized PVC was hydrophobic, with a measured mean ± standard deviation WCA of 96.7 ± 3.6° for PVC-DINCH and 110.2 ± 5.8° for PVC-TOTM. Plasma post-treatment and thermal post-treatment were respectively associated with a mean decrease in migration of 38.3 ± 1.9% for DINCH and 61.5 ± 4.4% for TOTM. Our results are promising with regard to limiting the migration of plasticizers into the patient's blood and thus enabling the development of safer medical devices.

Medical devices used in NICU: The main source of plasticisers' exposure of newborns.

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.

Factors influencing accuracy when preparing injectable drug concentrations in appliance with clinical practice: a norepinephrine case study.

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.

Sleep Medication in Older Adults: Identifying the Need for Support by a Community Pharmacist.

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.

Analysis of clinical pharmacist interventions in the COVID-19 units of a French university hospital.

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.

Reply to Otter et al. Comment on "Bernard et al. Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management. Metabolites 2021, 11, 252".

The comments written by R. Otter et al. [...].

Case report: risk of skin necrosis related to injectable vancomycin in critically ill newborn infants.

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 < 2.5 mg/mL via a peripheral intravenous catheter if a central venous catheter is not available.

Risk factors associated with unintentional medication discrepancies at admission in an internal medicine department.

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.

Optimising an Infusion Protocol Containing Cefepime to Limit Particulate Load to Newborns in a Neonatal Intensive Care Unit.

BACKGROUND: In neonatal intensive care units (NICUs), the simultaneous administration of drugs requires complex infusion methods. Such practices can increase the risk of drug incompatibilities resulting in the formation of a particulate load with possible clinical consequences. METHODS: This paper evaluates strategies to reduce the particulate load of a protocol commonly used in NICUs with a potential medical incompatibility (vancomycin/cefepime combination). The protocol was reproduced in the laboratory and the infusion line directly connected to a dynamic particle counter to evaluate the particulate matter administered during infusion. A spectrophotometry UV assay of cefepime evaluated the impact of filters on the concentration of cefepime administered. RESULTS: A significant difference was observed between the two infusion line configurations used in the NICU, with higher particulate load for cefepime infused via the emergency route. There was no change in particulate load in the absence of vancomycin. A filter on the emergency route significantly reduced this load without decreasing the cefepime concentration infused. Preparation of cefepime seemed to be a critical issue in the protocol as the solution initially contained a high level of particles. CONCLUSION: This study demonstrated the impact of a reconstitution method, drug dilution and choice of infusion line configuration on particulate load.

Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management.

Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates' exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers' exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients' urinary levels of each plasticizers' metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites' toxicity.

Long-term stability of ready-to-use norepinephrine solution at 0.2 and 0.5 mg/mL.

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.

Long-term stability of ready-to-use 1-mg/mL midazolam solution.

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.

New SPE-LC-MS/MS method for the simultaneous determination in urine of 22 metabolites of DEHP and alternative plasticizers from PVC medical devices.

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 <20%. The clinical applicability and suitability of our new method was assessed in patients in a neonatal intensive care unit to measure urinary concentrations of DEHP and alternative plasticizer metabolites. These metabolites were found in the majority of urine samples, with a median detection frequency of 95.2% (ranging from 12.5% to 100%). The high sensitivity, selectivity and ruggedness make the method suitable for large-scale biomonitoring studies of high-risk and general populations.

Effect of multi-lumen perfusion line on catheter-related bacteremia in premature infants: study protocol for a cluster-randomized crossover trial.

BACKGROUND: Catheter-related bacteremia (CRB) is the most frequent nosocomial infection in neonatal intensive care unit (NICU) patients, especially in very low-birth-weight infants. Administration of injectable drugs in premature newborn infants has many particularities and several types of infusion incidents have been reported. The Edelvaiss® Multiline NEO device is a novel multi-lumen access infusion device adapted to the specificities of infusion in neonatology. This multicenter, randomized, controlled study was therefore designed to determine whether or not Edelvaiss® Multiline NEO reduces the risk of CRB in preterm newborn infants in an NICU. METHODS/DESIGN: This is a multicenter, randomized, controlled trial, using a cluster-randomized crossover design. Four investigator centers (four clusters) will participate in the study and will be randomized into two groups, corresponding to two different sequences (either the Edelvaiss® Multiline NEO or standard infusion system sequence, then vice versa). A total of 280 patients will be recruited. Infants will be enrolled in the study at the time of placing a single-lumen central venous catheter. Three visits recording specific data are planned in the study protocol. The primary outcome measure is the incidence density (ID) of CRB. For each patient, the total number of catheters and CRB incidents as well as the duration of stay in the NICU will be computed and considered for analysis. DISCUSSION: The study will provide high-quality evidence to determine whether the Multiline NEO device reduces the risk of CRB in preterm newborns in NICUs or not. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02633124 . Registered on 7 December 2015.

In vitro assessment of the influence of intravenous extension set materials on insulin aspart drug delivery.

Insulin is a frequently prescribed drug in hospitals and is usually administered by syringe pumps with an extension line which can be made of various materials. Two insulin solutions were studied: an insulin analogue, Novorapid® which contains insulin aspart and two phenolic preservatives (e.g. phenol and metacresol) and Umuline rapide® with human insulin and metacresol as preservative. Some studies have indicated interactions between insulin, polyvinyl chloride (PVC) and polyethylene (PE). The aim of this work was to study such interactions between Novorapid® or Umuline rapide® and infusion extension line materials (PVC, PE and coextruded (PE/PVC)). Insulin solution at 1 IU/mL was infused at 2 mL/h over 24 hours with 16 different extension lines (8 in PVC, 3 in PE and 5 in PE/PVC). Ultra-Fast Liquid Chromatography with diode array detection (UFLC-DAD) was performed to quantify insulin (human and aspart) and preservatives (metacresol and phenol). Limited human insulin sorption was observed thirty minutes after the onset of infusion: 24.3 ± 12.9%, 3.1 ± 1.6% and 18.6 ± 10.0% for PVC, PE and PE/PVC respectively. With insulin aspart, sorption of about 5% was observed at the onset of infusion for all materials. However, there were interactions between phenol and especially metacresol with PVC, but no interactions with PE and PE/PVC. This study shows that insulin interacts with PVC, PE and PE/PVC at the onset of infusion. It also demonstrates that insulin preservatives interact with PVC, which may result in problems of insulin conservation and conformation. Some more studies are required to understand the clinical impact of the latter during infusion.

Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol.

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 < 0.001). Larger particles of ≥10 and 25 µm were also significantly reduced. Adding an extension set to the egress of the in-line filter (V = 1.7 mL) caused a significant increase in particulate contamination for both. This study showed that in-line filtration is an effective tool in preventing particle administration to patients. Their position in the infusion in-line is therefore important because of its impact on internal volume and drug particle formation.

How to solve the problem of co-elution between two compounds in liquid chromatography through the first UV derivative spectrum. A trial on alternative plasticizers to di(2-ethylhexyl) phthalate.

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 750µg/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.