Analysis of plasticizers in PVC medical devices: Performance comparison of eight analytical methods.

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.

Analytical methods for the determination of DEHP plasticizer alternatives present in medical devices: a review.

Until 2010, diethylhexylphthalate (DEHP) was the plasticizer most commonly used to soften PVC medical devices (MDs), because of a good efficiency/cost ratio. In flexible plasticized PVC, phthalates are not chemically bound to PVC and they are released into the environment and thus may come into contact with patients. The European Directive 2007/47/CE, classified DEHP as a product with a toxicity risk and restricted its use in MDs. MD manufacturers were therefore forced to quickly find alternatives to DEHP to maintain the elasticity of PVC nutrition tubings, infusion sets and hemodialysis lines. Several replacement plasticizers, so-called "alternative to DEHP plasticizers" were incorporated into the MDs. Nowadays, the risk of exposure to these compounds for hospitalized patients, particularly in situations classified "at risk", has not yet been evaluated, because migrations studies, providing sufficient exposure and human toxicity data have not been performed. To assess the risk to patients of DEHP plasticizer alternatives, reliable analytical methods must be first developed in order to generate data that supports clinical studies being conducted in this area. After a brief introduction of the characteristics and toxicity of the selected plasticizers used currently in MDs, this review outlines recently analytical methods available to determine and quantify these plasticizers in several matrices, allowing the evaluation of potential risk and so risk management.

[Physicochemical stability study of injectable solutions of cisatracurium besilate in clinical conditions]. / Stabilité physico-chimique des solutions injectables de bésilate de cisatracurium dans les conditions cliniques d'utilisation.

OBJECTIVES: To assess the stability of cisatracurium besilate solution stored at 5°C and 25°C. MATERIALS AND METHODS: Cisatracurium solutions at 2, 5 and 0.1mg/mL in 0.9 % sodium chloride or 5 % glucose were exposed to 5°C and 25°C under 60 % relative humidity for seven days. The physicochemical stability was assessed at 24, 48hours and seven days with dosage of the active substance, detection of degradation products and a possible racemization, measuring pH, osmolality and turbidity, assessment of coloration, visible particles and invisible particles count. RESULTS: Cisatracurium besilate present good stability for 24hours at 5°C and 25°C for concentrations between 0.1 and 5mg/mL. Beyond 24hours, the solutions at 2 and 5mg/mL remained stable for seven days at 5°C. At 25°C, potentially toxic degradation products appear in solutions of 0.1mg/mL between 24 and 48hours. No racemization was detected, the drug remains in its active form cis. CONCLUSION: Cisatracurium solutions at 2 and 5mg/mL may be stored at 5°C or 25°C for seven days. It's advisable to keep the solutions in a dilution of 0.1mg/mL in 0.9 % sodium chloride or 5 % glucose in the refrigerator. No diluted solution should be stored at room temperature beyond 24hours.

A pharmacokinetic study of 48-hour sevoflurane inhalation using a disposable delivery system (AnaConDa®) in ICU patients.

BACKGROUND: Little is known regarding sevoflurane kinetics and toxicity during long-term sedation of intensive care unit (ICU) patients using the AnaConDa® system. The objective of the present study was to establish a pharmacokinetic description of 48-h sevoflurane administration, and to estimate plasma concentrations of metabolites. METHODS: Forty-eight hour sedation with sevoflurane vaporized via an AnaConDa® device, with an end-tidal concentration objective of 1.5% (v/v), was initiated in 12 non-obese patients who did not have hepatic or renal failure but who required sedation for more than 48 h in our ICU. Plasma sevoflurane, hexafluoroisopropanol, and fluoride concentrations were determined over this time period and pharmacokinetic analysis was performed. RESULTS: The mean plasma concentration of sevoflurane was 76 mg/L at 24 h and 70 mg/L at 48 h. Wash-out of plasma sevoflurane correlated with a rapid decrease in the mean end-tidal sevoflurane level. The mean free plasma fraction of hexafluoroisopropanol never exceeded 8 mg/mL. The mean fluoride concentration was 0.8 µmol/L on day 0, 51.7 µmol/L on day 1, and 68.1 µmol/L on day 2 (P<0.0001). The distribution volume was 53 L, the elimination constant 2.9 h-1, the transfer constant from compartment 1 to compartment 2 (K1-2) 1.2 h-1, the K2-1 0.26 h-1, the half-life of elimination 3.78 h, and the total clearance 156 L/h. CONCLUSION: Following 48 hours of sedation using sevoflurane inhalation administered using an AnaConDa® delivery device, sevoflurane washout was rapid. Plasma fluoride levels accumulated over the study period without apparent nephrotoxicity.

[Stability and compatibility of acetaminophen, ketoprofen and amoxicillin in a fail-safe intravenous administration set]. / Stabilité et compatibilité du paracétamol, du kétoprofène et de l'amoxicilline administrés avec un perfuseur de sécurité

OBJECTIVES: Intravenous infusion takes an important place in the current therapy in hospitals and pharmaceutical firms keep improving their infusion medical devices, particularly with the development of an intravenous administration set with an automatic infusion stop. The aim of our study consists in an evaluation of the stability of acetaminophen, ketoprofen and amoxicillin during infusion and stasis of drugs for several hours in the dropper chamber and in the tube of this device. STUDY DESIGN: Analytical study. MATERIALS AND METHODS: Ten milligram per millilitre acetaminophen (acetaminophen 1 and acetaminophen 2), 1 mg/mL ketoprofen and 20 mg/mL amoxicillin were prepared and infused individually and successively with the intravenous administration set under ambient light and temperature. Collected samples of each drug during the infusion and after 24 hours of stasis in the medical device were monitored by a visual inspection, pH and osmolality assessment and chromatographic analysis of each drug with a validated stability-indicating method. RESULTS: Repeated individual perfusions of 10 mg/mL acetaminophen 1 or 1 mg/mL ketoprofen are possible through a fail-safe intravenous administration set, while repeated individual amoxicillin infusions are not because of the unstability of this drug. There is also no problem to infuse successively acetaminophen and ketoprofen through this medical device because these drugs are stable. However, we underlined an incompatibility between acetaminophen 2 and ketoprofen, which advises against the use of intravenous administration set for successive infusions of these two drugs. CONCLUSION: Despite the technical innovation of a fail-safe intravenous administration set, we have to stay aware of mixture consequences in intravenous infusion field.

Proton pump inhibitor administration via nasogastric tube in pediatric practice: comparative analysis with protocol optimization.

Proton pump inhibitors (PPIs) are largely prescribed to children because their efficacy and tolerance are now well-established. One disadvantage resides in the absence of liquid form which causes problems for their administration in nasogastric tubes. Indeed, the absence of use recommendations involves many misuses responsible for inefficiency and/or tube obstruction. We tried to evaluate if PPIs can be administered through pediatric nasogastric tubes. We administered four PPIs (Omeprazole, esomeprazole, lansoprazole and lansoprazole orally disintegrating tablet) through nasogastric tubes. For each PPI a study plan was drawn up to assess the influence of different variables: the volume of water to dissolve or put in suspension the PPIs (2ml or 5ml), the volume of tube flush-through water post-PPI administration (2ml, 5ml or 10ml), the length (50cm or 125cm) and the diameter (6 or 8 French) of the polyurethane tubes. For each assay an analysis of each active ingredient at the tube outlet by UV spectrometry was carried out. All 6 F tubes were obstructed by PPIs. Through 8 F tubes, we observed a mean recovery of active ingredient of 86.2% for lansoprazole orally disintegrating tablet, 36.9% for esomeprazole but only 7.1% for lansoprazole and 3.9% for omeprazole. It is disadvised using omeprazole and lansoprazole through 8 F nasogastric tubes because no condition ensures the transit of an efficient concentration of active ingredient. For esomeprazole, the best conditions of administration were a water volume of 5ml and a rinse volume of 5ml but only a half of the microgranules administered were recovered. The most satisfactory results were obtained with lansoprazole orally disintegrating tablet. A 5ml volume of water diluent for suspension and a 10ml volume of flush-through water made it possible to deliver the full lansoprazole dose administered.