A proof of principle study using radiopharmaceuticals to quantify and localize container-content interactions in medical syringes.

The sorption of drugs onto their contents is a known phenomenon that is difficult to analyse precisely. The purpose of this study was to present a non-invasive method for locating and quantifying sorption phenomena using radiopharmaceuticals. Radiopharmaceutical are medicines armed with a radionuclide enabling quantification and imaging using dedicated scanners. The sorption of nine different radiopharmaceuticals on 2- and 3-part syringes was investigated. These syringes were filled with the studied radiopharmaceutical solutions and stored immobile for 3 h. At different times ranging from 0 to 180 min, 10 µL were taken from the syringes and the radioactivity of these samples was determined by a gamma counter. 5 radiopharmaceuticals exhibited no significant sorption at any time point in both 2 and 3-parts syringes, but 4 radiopharmaceuticals exhibited sorption losses varying from 20 to 33% after 3 h contact with 3-part-syringes, but no sorption on 2-part syringes at any time point. [99mTc]Tc-tetrofosmine Single Photon Emission Computed Tomography/Computed Tomography imaging indicated clearly that the interactions were located on the rubber plunger of the 3-part-syringes. The specific nature of radiopharmaceuticals allowed their use as an innovative method to quantify and localize drug sorption phenomena.

[Infusion sets in neonatology: What practices in France?] / Montages de perfusion en néonatologie : quelles pratiques en France ?

OBJECTIVES: Therapeutic management of ill newborns can require complex infusion practices using medical devices (MD). Currently, there does not exist any recommendations concerning these infusion practices. The objective of this work was to study and characterise French infusion methods neonatal and neonatal intensive care units. MATERIALS AND METHODS: The study was performed in 2019, during 6 months. French hospitals possessing high (type 3) or medium (type 2B) grade maternity ward were contacted and asked to complete a 5 part online survey, to gather general information about the hospital/ward, infusion methods (overall and detailed), and detailed information about the medications and MD used. RESULTS: The participation level was of 19.6 % Type 3 maternities use overall two-times more MD than those of type 2B. The vascular access device most commonly used was a single lumen catheter (80.6 % of infusion methods). 100 % of the hospitals having answered used multi-access devices (three-way tap, multiport infusion manifold, Y-extension lines) and 93.5 % used a pump-infusor. Lipidic filters for parenteral nutrition were used in 78.6 % of the hospitals. Two general standard of infusion methods were isolated: a simple version with two access points (type 2B hospitals), and a complex one with five access points (from hospitals with type 3 maternities). CONCLUSIONS: Neonatal infusion practices in France are very heterogeneous, thus exposing the patients to a degree of variability during their therapeutic management. This work is a first step forwards to help analyse and anticipate the risks of content/container interactions caused by infusion practices.

On-call duties in hospital pharmacies: National survey and elaboration of a training program for pharmacy residents.

OBJECTIVES: During their residency, pharmacy residents are required to attend a hospital on-call program in order to insure the continuum of care for inpatients. This activity is subject to risks, and requires a prior training. Our aim was to develop and to optimize such a training program. METHODS: To this end, we first established a baseline study of the existing training methods in our hospital and those in the different hospitals of France in which pharmacy residents realize in-house on-call duties, associated with an identification of both pharmacists and students' needs in our institution. These preliminary studies were used to create a transversal, structured and harmonized training program. RESULTS: The results of our national survey highlighted great disparities of training between the establishments and point out the lack of structure, organization and harmonization of the training, which residents expected to be improved. Our training program contains 3 parts: initial theoretical training, initial practical training and continuous training. Beyond the harmonization of the theoretical training's materials between the different sectors of the pharmacy, new tools were introduced like an in-house on-call duty notebook complementary to trainings adapted to note taking, simulation's workshops and interactive quizzes. The training was gradually implemented in our hospital pharmacy, in collaboration with the pharmacists of the different activity sectors. CONCLUSIONS: The next steps of our work will be to assess pharmacists and pharmacy residents' satisfaction about our program and its efficacy.

Impact of alternative materials to plasticized PVC infusion tubings on drug sorption and plasticizer release.

Medical tubings in plasticized polyvinylchloride (PVC) are widely used for the infusion of medications but are known in some cases to cause content-container interactions (drug sorption and plasticizer release). The aim of this study was to assess interactions between drugs and five alternative materials to a reference plasticized PVC intravenous (IV) infusion tubing: three were PVC coextruded with polyethylene (PE), polyurethane (PU) or a thermoplastic elastomer (Styrene-EthyleneButadiene-Styrene (SEBS)) and two were SEBS or thermoplastic olefin (TPO) monolayer tubings. Diazepam and insulin were chosen as respective reference of absorption and adsorption while paracetamol acted as a negative control. The concentration of each drug was quantified with liquid chromatography to evaluate a potential loss after a static contact condition and simulated infusion at 1 mL/h and 10 mL/h dynamic condition by an electric syringe pump. A characterization of each material's surface was performed by Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and by measurement of surface zeta potential. Plasticizer release was quantified by gas chromatography coupled with mass spectrometry (GC-MS). For all tubings except PVC/PU, no loss of paracetamol was observed in any condition. Diazepam sorption appeared to be less important with PVC/PE, PVC/SEBS, SEBS and TPO tubings than with PVC, but was more important when using PVC/PU tubings. PVC tubings induced the least loss of insulin amongst all the studied materials. Surface analysis by ATR-FTIR highlighted the presence of a plasticizer (that could be attributed to Tris (2-Ethylhexyl) Trimellitate (TOTM)) in the coextruded SEBS layer of PVC/SEBS, which could have influenced drug sorption, probably as a consequence of a migration from the PVC layer. Coextruded PVC/SEBS and PVC/PE presented the lowest zeta potential of all studied materials with respective values of -39 mV and -36 mV and were related to the highest sorption of insulin while PVC/PU with the highest zeta potential (about -9 mV) presented the highest absorption of diazepam. Coextruded layered materials appeared to have a lower plasticizer release than PVC alone. As a conclusion, PVC/PE and thermoplastic elastomers alone or coextruded with PVC could be interesting alternatives to PVC tubings with regards to sorption phenomena and plasticizer release.

[Pharmacist's interview with type 2 diabetes: Development of a follow-up form]. / L'entretien pharmaceutique pour le patient diabétique de type 2 : élaboration d'une fiche de suivi.

OBJECTIVES: Type 2 diabetes is a major public health concern because of its prevalence, the severity of complications and the financial implications. Compliance and patient's autonomy in medications intake play key roles in the success of treatment. Pharmacists' interviews ensure an optimized and individual follow-up. Type 2 diabetes is not one of the targeted diseases to perform pharmacists' interviews on under Health Insurance. We thus judged useful to contribute to their development. METHODS: We applied a cross-disciplinary methodological process in order to define the specifications of the follow-up form useful to conduct the pharmacist's interview 1 by focusing on the identification of a non-compliance and its origins. A feasibility study was carried out in order to check its workability to the pharmacy practice. RESULTS: The follow-up form, associated with a pharmacist practical guide, includes 3 parts: (1) General informations, (2) Survey establishing patient's knowledge, (3) Summary including a level of knowledge assessment grid. Outcomes provide a long but appropriate-felt duration, few difficulties to conduct the interview and a proven usefulness in 90% of all cases that make the follow-up form suitable to the pharmacy practice. CONCLUSIONS: This tool could serve as a model for the pharmacist to conduct his future interviews for the type 2 diabetes patients, thus improving patient care, together with other health professionals.

Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions.

Cyclosporine A eye drops are used at concentrations ranging from 0.5 to 20mg/mL to treat a variety of ophthalmic diseases. Cyclosporine A formulations at high concentrations are difficult to manufacture because of cyclosporine's lipophilicity, and generally require an oil based vector. In this study, we investigated the physicochemical and microbiological stability of two high concentrations (10mg/mL and 20mg/mL) of an ophthalmic cyclosporine A micellar solution in a low density polyethylene multidose eyedropper, at two conservation conditions (5°C and 25°C), before and with simulated use. Analyses used were the following: visual inspection, cyclosporine quantification by a stability-indicating liquid chromatography method, osmolality and pH measurements and turbidity. A complementary analysis by dynamic light scattering was implemented to evaluate potential particle formation or micelle size change. In the in-use study, cyclosporine quantification was also performed on the drops emitted from the multidose eyedroppers. Our results show that the cyclosporine micellar formulation retains good physicochemical and microbiological stability, as all parameters stayed within acceptable range limits, however a higher variability in cyclosporine concentrations was observed for 20mg/mL units stored at 25°C. The in-use study showed that cyclosporine concentrations in the emitted drops were also within acceptable range limits. The micellar formulation presented in this study can therefore be stored at 5°C or at ≤25°C for up to 6months.

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.

[Security of hospital infusion practices: From an a priori risk analysis to an improvement action plan]. / Sécurisation de la perfusion en milieu hospitalier : de l'analyse de risques a priori au plan d'action d'amélioration des pratiques.

OBJECTIVES: Infusion in care units, and all the more in intensive care units, is a complex process which can be the source of many risks for the patient. Under cover of an institutional approach for the improvement of the quality and safety of patient healthcare, a risk mapping infusion practices was performed. METHODS: The analysis was focused on intravenous infusion situations in adults, the a priori risk assessment methodology was applied and a multidisciplinary work group established. RESULTS: Forty-three risks were identified for the infusion process (prescription, preparation and administration). The risks' assessment and the existing means of control showed that 48% of them would have a highly critical patient security impact. Recommendations were developed for 20 risks considered to be most critical, to limit their occurrence and severity, and improve their control level. An institutional action plan was developed and validated in the Drug and Sterile Medical Devices Commission. CONCLUSION: This mapping allowed the realization of an exhaustive inventory of potential risks associated with the infusion. At the end of this work, multidisciplinary groups were set up to work on different themes and regular quarterly meetings were established to follow the progress of various projects. Risk mapping will be performed in pediatric and oncology unit where the risks associated with the handling of toxic products is omnipresent.

Migration of plasticizers from PVC medical devices: Development of an infusion model.

Alternatives to DEHP plasticizers are used in various PVC medical devices (MD) for infusion. As they are able to migrate from these MDs into infused solutions, they may come into contact with patient. Different and specific clinical parameters influence their migration in at-risk situations such as infusion. In contrast to the regulations for Food Contact Materials (MCDA), there is currently no acceptable migration limits for the use of these plasticizers in clinical situations. In order to assess their migration, and thus control the risks linked to these MDs, we developed a migration model for the plasticizers in MDs. To this end, we applied a cross-disciplinary methodological process similar to that used in the food-processing industry, taking into account the MDs' conditions of use in clinical practice. The simulation model is simple and includes the following conditions: MD should be tested with a dynamic method that respects our established clinical assumption (2 L of infused solutions via 13 dm(2) of plasticized PVC), at a temperature of 25 °C and during 24 h of contact, using a 50/50 (v/v) ethanol/water simulant. This model could be proposed as a tool for the safety evaluation of the patients' exposure risk to plasticizers from PVC medical devices for infusions.

Migrability of PVC plasticizers from medical devices into a simulant of infused solutions.

Medical devices (MD) for infusion and artificial nutrition are essentially made of plasticized PVC. The plasticizers in the PVC matrix can leach out into the infused solutions and may enter into contact with the patients. In order to assess the risk of patient exposure to these plasticizers we evaluated the migration performance of DEHP, DEHT, DINCH, and TOTM using a model adapted to the clinical use of the MDs. Each PVC tubing sample was immersed in a simulant consisting of a mixture of ethanol/water (50/50v/v) at 40°C and migration tests were carried out after 24h, 72h, and 10 days.DEHP had the highest migration ability, which increased over time. The amount of TOTM released was more than 20 times less than that of DEHP, which makes it an interesting alternative. DEHT is also promising, with a migration level three times smaller than DEHP. However, the migration ability of DINCH was similar to DEHP, with the released amounts equaling 1/8th of the initial amount in the tubing after 24h of contact. Taking into account the available toxicological data, TOTM and DEHT appear to be of particular interest. However, these data should be supplemented and correlated with clinical and toxicological studies on plasticizers and their metabolites.

[Impact of a targeted educational intervention on respiratory syncytial virus bronchiolitis prevention in full-term and preterm infants]. / Optimisation de la prévention de la bronchiolite à VRS chez les nouveaux-nés à risque et les prématurés : mesure de l'impact d'une intervention éducative ciblée.

OBJECTIVES: Palivizumab, a humanized monoclonal antibody directed against respiratory syncytial virus (RSV), is the only existent immunoprophylaxis therapy for prevention of serious lower respiratory tract disease caused by RSV in infants (up to 2 years of age), particularly in those who meet high-risk criteria (preterm infants and/or those with bronchopulmonary or congenital heart disease). In our region, the monthly injections are not given at the hospital but by private pediatricians during the epidemic season. We aimed to assess the influence of an educational and personalized support of preterm infants treated with Palivizumab on patient compliance during the last season. METHODS: A three-level educational intervention was conducted: the parents were advised in the neonatology units, then at the hospital pharmacy where the treatment was delivered, and finally by their referent pediatrician. We evaluated the impact of this intervention by measuring patient compliance, defined by two criteria, and by measuring the rate of rehospitalization for RSV bronchiolitis. We compared these results to those of the previous season (2011-2012) in which no interventional program was conducted. RESULTS: Compliance was better in the group of patients followed (2012-2013); 59.7% of them received all the palivizumab doses, while only 32.9% of the infants not followed received all doses. The number of injections given at appropriate intervals remained stable between the two groups and no significant difference was found in the rate of RSV bronchiolitis rehospitalizations. CONCLUSION: This educational intervention program, coordinated by doctors and pharmacists, is associated with improved treatment compliance in high-risk of RSV bronchiolitis infants. To optimize such a care program, we have planned to set up and then evaluate a call center procedure involving extensive counseling for parents and reminder telephone calls.

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.

Modification of the surfaces of medical devices to prevent microbial adhesion and biofilm formation.

BACKGROUND: The development of devices with surfaces that have an effect against microbial adhesion or viability is a promising approach to the prevention of device-related infections. AIM: To review the strategies used to design devices with surfaces able to limit microbial adhesion and/or growth. METHODS: A PubMed search of the published literature. FINDINGS: One strategy is to design medical devices with a biocidal agent. Biocides can be incorporated into the materials or coated or covalently bonded, resulting either in release of the biocide or in contact killing without release of the biocide. The use of biocides in medical devices is debated because of the risk of bacterial resistance and potential toxicity. Another strategy is to modify the chemical or physical surface properties of the materials to prevent microbial adhesion, a complex phenomenon that also depends directly on microbial biological structure and the environment. Anti-adhesive chemical surface modifications mostly target the hydrophobicity features of the materials. Topographical modifications are focused on roughness and nanostructures, whose size and spatial organization are controlled. The most effective physical parameters to reduce bacterial adhesion remain to be determined and could depend on shape and other bacterial characteristics. CONCLUSIONS: A prevention strategy based on reducing microbial attachment rather than on releasing a biocide is promising. Evidence of the clinical efficacy of these surface-modified devices is lacking. Additional studies are needed to determine which physical features have the greatest potential for reducing adhesion and to assess the usefulness of antimicrobial coatings other than antibiotics.

In vitro evaluation of TiO2 nanotubes as cefuroxime carriers on orthopaedic implants for the prevention of periprosthetic joint infections.

CONTEXT: The prevention of periprosthetic joint infections requires an antibiotic prophylactic therapy, which could be delivered locally using titanium dioxide nanotubes as novel reservoirs created directly on the orthopaedic implant titanium surface. OBJECTIVE: In this study, the influence of several parameters that could impact the use of titanium dioxide nanotubes as cefuroxime carriers was investigated. METHOD: Cefuroxime loading and release was studied for 90 min with three nano-topography conditions (nano-smooth, nano-rugged and nano-tubular), two cefuroxime loading solution concentrations (150 mg/mL and 25mg/mL) and two nano-tubular crystalline structures. RESULTS: In all tested conditions, maximum amount of cefuroxime was obtained within 2 min. For both cefuroxime loading solution concentrations, nano-smooth samples released the least cefuroxime, and the nano-tubular samples released the most, and a six-fold increase in the concentration of the cefuroxime loading increased the amount of cefuroxime quantified by more than seven times, for all tested nano-topographies. However, the nano-tubes' crystalline structure did not have any influence on the amount of cefuroxime quantified. CONCLUSION: The results demonstrated that the surface nano-topography and loading solution concentration influence the efficiency of titanium dioxide nanotubes as cefuroxime carriers and need to be optimized for use as novel reservoirs for local delivery of cefuroxime to prevent periprosthetic infections.

[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.

Stability and compatibility of a mixture of the anti-cancer drugs etoposide, cytarabine and daunorubicine for infusion.

We evaluated (i) the stability of a mixture of the three anti-cancer agents used for the treatment of leukemia, namely etoposide, cytarabine and daunorubicine, in 5% glucose, and (ii) its compatibility towards various materials during an infusion protocol as performed for therapeutic purposes in hospital practice. Etoposide and cytarabine were assayed by high-performance liquid chromatography with a C18 type column and UV detection. Daunorubicine was assayed by visible spectrophotometry. The stability study showed all three anti-cancer drugs to be stable in 5% glucose solution, both alone and mixed. Best conservation was obtained by keeping bottles containing the mixture in the dark at room temperature. During the infusion protocol used in clinical practice, etoposide, cytarabine and daunorubicine were stable and compatible with the various materials present in the infusion sets and extension tubing (polyvinyl chloride, polyethylene) and catheters (silicone). Observed variations in concentration did not exceed 10% of initial concentrations of each drug, though we would advocate changing infusion sets and extension tubing daily.

Solid-phase extraction of isosorbide dinitrate and two of its metabolites from plasma for gas chromatographic analysis.

A rapid, accurate and selective method for the determination of isosorbide dinitrate and its 2- and 5-isosorbide mononitrate metabolites in 1.0 ml of human plasma has been developed. Before chromatographic quantitation by gas-liquid chromatography with electron-capture detection, the compounds are subjected to solid-phase extraction, using ENVI 18 cartridges (Supelco). The intra-day and inter-day coefficients of variation are less than 10%, except the inter-day coefficient of variation for the assay of 5-isosorbide dinitrate which is less than 15%. Limits of quantitation are 10, 10 and 20 ng/ml for isosorbide dinitrate, 2-isosorbide mononitrate and 5-isosorbide mononitrate, respectively. Recoveries are in excess of 90% for isosorbide dinitrate and 70% for its two metabolites.

[Analysis of opiates in the urine of children with gas chromatography coupled to mass spectrometry]. / Analyse des opiacés dans les urines chez les enfants par chromatographie en phase gazeus couplée à la spectrométrie de masse.

Acute intoxication by opiates is quite frequent and very serious, especially in children whence the need to assay these compounds in biological fluids. The authors have developed an assay for opiates (codeine, codethyline, morphine and pholcodine) by gas chromatography/mass spectrometry (GC/MS) on a capillary column. This assay can identify different opiates due to its high specificity. Before chromatography, urine from children undergoes acid hydrolysis and solid phase extraction. The compounds are derivatized by acetylation before being chromatographied. This assay is carried out after a first search for opiates in urine by immunoenzymology. Each sample containing opiates is then analysed by GC/MS in order to determine specifically the opiates responsible for intoxication.