Development and application of a protocol for extractables profiling from central venous catheters in neonates.

Peripherally inserted central catheters (PICC-lines) used in neonatology are made of thermoplastic polyurethane (TPU) or silicone. These materials usually contain substances that may leach into drug vehicles or blood. In this extractables study, we determined the optimal extraction conditions using TPU films containing defined amounts of butylhydroxytoluene (BHT) and then applied them on unused and explanted PICC-lines. Maceration and sonication tests were carried out with hexane, acetone and water as the extraction solvents. The analyses were performed using gas and liquid chromatography coupled with mass spectrometry detectors, as well as inductive coupled plasma optical emission spectroscopy to detect a wide range of extractables. We selected a limited list of substances to be sought from the usual adjuvants and monomers, related to their carcinogenic, mutagenic or reprotoxic properties and/or existence in endocrine disruptors lists. The TPU-film experiments showed that acetone was slightly better than hexane, and maceration better than sonication. When applied to PICC-lines, the extraction methods were almost similar but acetone was clearly better than hexane for TPU. From the 48 peaks initially observed in GC-MS, we ended up with 37 peaks to follow in TPU PICC-lines, among which were those of BHT and 4,4'-Methylenebis(cyclohexyl isocyanate) isomers. For silicone PICC-lines, out of 41 peaks initially observed in GC-MS, we followed 20 peaks, most of them being identified as cyclosiloxanes. Barium was the main inorganic element extracted for both PICC-lines. For TPU PICC-lines, the inter-batch variability was higher than for intra-batch, but in silicone devices both were similar. When compared to new PICC-lines, explanted TPU PICC-lines extracted peaks had a lower area under the curve (AUC), while the AUCs of the peaks were higher for the majority of silicone PICC-lines extract compounds. No identified substances were detected above their toxicological threshold, but isocyanates and cyclosiloxanes toxicity was mostly studied for other exposition routes than intravenous. The methods defined in this study were efficient in producing extractable profiles from both PICC-lines.

Comparative Study of Sorption Phenomena Between Three Medications and Syringes Made of Cyclic Olefin Copolymer or Polypropylene.

INTRODUCTION: Medical syringes are widely used in hospitals to store and administer drugs, and the contact time between the drugs and these syringes can vary from a few minutes to several weeks like for pharmaceutical preparations. The aim of this comparative study was to evaluate the potential sorption phenomena occurring between three drugs (paracetamol, diazepam and insulin aspart) and polypropylene syringes (PP) or syringes made of Cyclic Olefin Copolymer (COC). MATERIALS AND METHODS: 50 mL 3-part syringes made of either COC with crosslinked silicone on the barrel inner surface (COC-CLS) and a bromobutyl plunger seal, or PP lubricated with silicone oil (PP-SOL) with a polyisoprene plunger seal were used. RESULTS: COC-CLS syringes induced less sorption of diazepam and insulin than PP-SOL syringes and the plunger seal material seemed to be the main cause of these interactions. An alkalinization of the medications in contact with the PP-SOL syringes was observed. It could be caused by leachable compounds and should be investigated further. CONCLUSION: This work shows once again that it is essential to consider content-container interactions to help improve the safe use of parenteral drugs.

[Comparative study of production and control processes of parenteral nutritional admixtures in neonatology]. / Étude comparative des processus de production et de contrôle analytique des préparations magistrales de mélanges nutritifs parentéraux en néonatalogie.

OBJECTIVES: To assess the impact of disparities in production and analytical control processes on the quality of parenteral nutrition (PN) preparations produced in the Auvergne-Rhône-Alpes region. METHODS: This study was carried out in four hospital pharmacies of the Auvergne-Rhône-Alpes region. To assess the impact of production processes, each centre produced ten PN preparations from the same prescription. Analytical controls (sodium, potassium and calcium dosage) were carried out on all the preparations. To assess the impact of the control processes, a batch of ten preparations was produced from the same prescription. Samples were sent to the four hospital pharmacies for analytical control (sodium, potassium and calcium dosage). RESULTS: Measurements of relative production bias show that there is a significant difference between the preparations from the four centres in terms of sodium and potassium content. Each centre had at least one production bias for one of the three electrolytes measured. Concerning analytical controls, there was a significant difference between the four centres in the sodium and potassium levels measured. With the exception of calcium, all the centres reported measurements within the usual specifications of±10% of the target value. The results obtained have no clinically significant impact. CONCLUSION: The diversity of NP practices has a real impact on the quality of the preparations made. A regional collaboration should be envisaged to standardise patient care.

Development and Stability of a New Formulation of Pentobarbital Suppositories for Paediatric Procedural Sedation.

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (-63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS.

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.

[Hospital - community pharmacy coordination for the dispensing of oral antineoplastic drugs: An observational study in the French county of the Aveyron]. / Lien ville-­hôpital et anticancéreux oraux : opinion des pharmaciens de l'Aveyron.

INTRODUCTION: The growing number of oral antineoplastic agents delivered by French community pharmacies has modified the job and roles of community pharmacists. Coordination between hospitals (oncology centers) and community pharmacies has become essential for a quality work in this field. The goal of this work was to obtain information about the feeling of the community pharmacies teams in a French county (Aveyron) regarding the communication tools offered by various hospitals with an oncology service (when receiving a beginning prescription for an oral antineoplastic drug), and to evaluate the impact of these tools on their practice. METHODS: A declarative survey was submitted to the 109 community pharmacies of this county to evaluate their relationship with their nearest oncology centers (including communication tools) and collect their opinion on the quality of the coordination and their pharmaceutical exercise. RESULTS: The response rate was of 54% (59 community pharmacies). Communication between the oncology centers and the pharmacies was limited (only 50% of the pharmacies received information complementary to the prescription), the available tools were not used very frequently (44% of pharmacies didn't use shared medical records) and there was a strong feeling of rupture between the pharmacies and the oncology centers, impacting the quality of their work (46% of respondents indicated being little or incapable of correctly validating the indication of the anticancer drug). DISCUSSION: This study illustrates the under-use of the available hospital-community pharmacy communication tools and the fact that the pharmacies feel difficulties to correctly deliver oral antineoplastic medications due to a lack of information.

Evaluation of color changes during stability studies using spectrophotometric chromaticity measurements versus visual examination.

Stability studies are essential to be able to assign an expiration date to medications. Color variation is one of the organoleptic characteristics of actives substances or medications which can indicate the presence of contaminations, impurities or degradations products. However there is no data available comparing the often used visual examination with spectrophotometric measurements during stability studies. The aim of this study was therefore to evaluate precisely how different the two methods are, by comparing the change of color of two drug formulations chosen as models, assessed by visual examination versus a spectrophotometric colorimetric analysis. Paracetamol and parenteral nutrition solutions were stored in stress conditions for up to 46 days, and were subjected to a visual examination using color reference solutions and to lightness and chromaticity measurement to determine their specific color by UV-Vis spectrophotometry. The color of paracetamol solutions changed faster when exposed to stress condition (light), as did the PNS when exposed to heat. In both cases, color variations were detected earlier and more precisely by UV-Vis spectrophotometry than by visual examination. Color measurement using an UV-Vis spectrophotometry should advantageously replace visual examination when assessing colors changes during drug stability studies.

Insulin Adsorption onto PE and PVC Tubings.

We investigate the adsorption of insulin onto PE and PVC materials by using HPLC measurements and computer simulations. We interpret the experiments by calculating the Gibbs free energy profiles during the adsorption process. The values of free energy of adsorption show a good agreement with the experimental measurements. The adsorption of insulin onto the different materials is characterized through the conformational changes with respect to its conformation in water and the interfacial regions, which are described by specific arrangements of polymer chains, water, insulin, and plasticizer molecules.

A Minireview on Brain Models Simulating Geometrical, Physical, and Biochemical Properties of the Human Brain.

There is a growing body of evidences that brain surrogates will be of great interest for researchers and physicians in the medical field. They are currently mainly used for education and training purposes or to verify the appropriate functionality of medical devices. Depending on the purpose, a variety of materials have been used with specific and accurate mechanical and biophysical properties, More recently they have been used to assess the biocompatibility of implantable devices, but they are still not validated to study the migration of leaching components from devices. This minireview shows the large diversity of approaches and uses of brain phantoms, which converge punctually. All these phantoms are complementary to numeric models, which benefit, reciprocally, of their respective advances. It also suggests avenues of research for the analysis of leaching components from implantable devices.

Ex Vivo Model to Assess the Exposure of Patients to Plasticizers from Medical Devices during Pre-CAR-T Cells' Apheresis.

BACKGROUND: The treatment of relapsed or refractory leukemia remains a major problem. Among the new therapeutic approaches, the use of modified T lymphocytes, called chimeric antigen receptor T cells (CAR-T cells), seems promising. The first step of their preparation is leukapheresis, which involves the collection of mononuclear cells from the patient. This medical procedure requires numerous medical devices (MDs) made of plasticized polyvinylchloride (PVC). These compounds can leach out of the devices during contact with the patient's blood. The aim of our study was to evaluate the migration of the plasticizers contained in the MD during a simulated pre-CAR-T cell leukapheresis procedure, and to measure the patient's and their lymphocytes' exposure to them. METHODS: The qualitative and quantitative composition of the MD used for pre-CAR-T cell apheresis was determined by gas chromatography-mass spectrometry (GC-MS). Then, an ex vivo leukapheresis model using an ethanol/water simulant was performed to evaluate the plasticizers' migration under simulated clinical conditions of pre-CAR-T cells' cytapheresis. The plasticizers released into the simulant were quantified by GC-MS. RESULTS: Diethylhexylphthalate (DEHP) was found in the apheresis kit, with amounts ranging from 25% to 59% (g/100 g of PVC). Bis(2-ethylhexyl) adipate was detected at trace levels. A total of 98.90 ± 11.42 mg of DEHP was released into the simulant, corresponding to an exposure dose of 1.4 mg/kg for a 70 kg patient. CONCLUSIONS: Patients undergoing a pre-CAR-T cell apheresis are mainly exposed to DEHP, which can impact their health because of its endocrine disruption effect, but could also lead to a decrease in CAR-T cells' efficiency/quality.

Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases.

Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C.

Cyclodextrins Allow the Combination of Incompatible Vancomycin and Ceftazidime into an Ophthalmic Formulation for the Treatment of Bacterial Keratitis.

Ceftazidime (CZ) and vancomycin (VA) are two antibiotics used to treat bacterial keratitis. Due to their physical incompatibility (formation of a precipitate), it is not currently possible to associate both molecules in a single container for ophthalmic administration. We firstly characterized the incompatibility then investigated if 2-hydroxypropyl-beta (HPßCD) and 2-hydroxypropyl-gamma cyclodextrins (HPγCD) could prevent this incompatibility. The impact of pH on the precipitation phenomena was investigated by analysing the supernatant solution of the mixture using high performance liquid chromatography. A characterization of the inclusion of CZ with HPγCD using 1H nuclear magnetic resonance (NMR), and VA with HPßCD using 1H-NMR and a solubility diagram was performed. A design of experiment was built to determine the optimal conditions to obtain a formulation that had the lowest turbidity and particle count. Our results showed that VA and CZ form an equimolar precipitate below pH 7.3. The best formulation obtained underwent an in-vitro evaluation of its antibacterial activity. The impact of HPCDs on incompatibility has been demonstrated through the inclusion of antibiotics and especially VA. The formulation has been shown to be able to inhibit the incompatibility for pH higher than 7.3 and to possess unaltered antibacterial activity.

Critical Drug Loss Induced by Silicone and Polyurethane Implantable Catheters in a Simulated Infusion Setup with Three Model Drugs.

Silicone and polyurethane are biocompatible materials used for the manufacture of implantable catheters, but are known to induce drug loss by sorption, causing potentially important clinical consequences. Despite this, their impact on the drugs infused through them is rarely studied, or they are studied individually and not part of a complete infusion setup. The aim of this work was to experimentally investigate the drug loss that these devices can cause, on their own and within a complete infusion setup. Paracetamol, diazepam, and insulin were chosen as models to assess drug sorption. Four commonly used silicone and polyurethane catheters were studied independently and as part of two different setups composed of a syringe, an extension set, and silicone or polyurethane implantable catheter. Simulated infusion through the catheter alone or through the complete setup were tested, at flowrates of 1 mL/h and 10 mL/h. Drug concentrations were monitored by liquid chromatography, and the silicone and polyurethane materials were characterized by ATR-IR spectroscopy and Zeta surface potential measurements. The losses observed with the complete setups followed the same trend as the losses induced individually by the most sorptive device of the setup. With the complete setups, no loss of paracetamol was observed, but diazepam and insulin maximum losses were respectively of 96.4 ± 0.9% and 54.0 ± 5.6%, when using a polyurethane catheter. Overall, catheters were shown to be the cause of some extremely high drug losses that could not be countered by optimizing the extension set in the setup.

Understanding and Characterizing the Drug Sorption to PVC and PE Materials.

Characterizing the sorption of drugs onto polyvinylchloride (PVC) and polyethylene (PE) materials in terms of thermodynamic adsorption properties and atomistic details (local arrangements, orientation, and diffusion) is fundamental for the development of alternative materials that would limit drug sorption phenomena and plasticizer release. Here, a combination of experiments and sophisticated calculations of potential of mean forces are carried out to investigate the sorption of paracetamol and diazepam to PE and PVC surfaces. The simulated Gibbs free energies of adsorption are in line with the experimental interpretations. The polymer-drug-water interface is then characterized at the molecular scale by an in-depth investigation of local properties such as density, orientation, and diffusion.

Stability of Ophthalmic Atropine Solutions for Child Myopia Control.

Myopia is an ophthalmic condition affecting more than 1/5th of the world population, especially children. Low-dose atropine eyedrops have been shown to limit myopia evolution during treatment. However, there are currently no commercial industrial forms available and there is little data published concerning the stability of medications prepared by compounding pharmacies. The objective of this study was to evaluate the stability of two 0.1 mg/mL atropine formulations (with and without antimicrobiobial preservatives) for 6 months in two different low-density polyethylene (LDPE) multidose eyedroppers. Analyses used were the following: visual inspection, turbidity, chromaticity measurements, osmolality and pH measurements, atropine quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, atropine quantification was also performed on the drops emitted from the multidose eyedroppers. All tested parameters remained stable during the 6 months period, with atropine concentrations above 94.7% of initial concentration. A breakdown product (tropic acid) did increase slowly over time but remained well below usually admitted concentrations. Atropine concentrations remained stable during the in-use study. Both formulations of 0.1 mg/mL of atropine (with and without antimicrobial preservative) were proved to be physicochemically stable for 6 months at 25 °C when stored in LDPE bottles, with an identical microbial shelf-life.

Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability?

Fungal keratitis is a sight-threatening disease for which amphotericin B eye drops is one of the front-line treatments. Unfortunately, there are currently no commercial forms available, and there is little data concerning the long-term stability of compounded formulations based on intravenous dosages forms. New formulations of amphotericin B ophthalmic solutions solubilised with γ-cyclodextrins have shown promising in-vitro results, but stability data is also lacking. The objective of this study was therefore to investigate the stability of a formulation of ready-to-use amphotericin B solubilised in 2-hydroxypropyl-γ-cyclodextrins (AB-HP-γ-CD), for 350 days. An amphotericin B deoxycholate (ABDC) formulation was used as a comparator. Analyses used were the following: visual inspection, turbidity, osmolality and pH measurements, amphotericin B quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. AB-HP-γ-CD formulation showed signs of chemical instability (loss of amphotericin B) after 28 and 56 days at 25 °C and 5 °C. Adding an antioxidant (ascorbic acid) to the formulation did not improve stability. ABDC formulation showed signs of physical instability (increased turbidy and amphotericin B precipitation) after 28 days and 168 days at 25 °C and 5 °C. As such, AB-HP-γ-CD formulation does not provide long-term stability for ophthalmic amphotericin B solutions.

Quantification of bis(2-ethylhexyl) phthalate released by medical devices during respiratory assistance and estimation of patient exposure.

Bis(2-ethylhexyl) phthalate (DEHP) migration from polyvinyl chloride (PVC) has been studied with infusion, transfusion and extracorporeal oxygenation devices, but no study has been conducted to estimate its migration via respiratory medical devices (MDs). This work aims to develop an ex vivo model to quantify DEHP released doses by these MDs, which will then be used to estimate newborns DEHP exposure from respiratory assistance MDs. We followed the Frensh National Research and Safety Institute (INRS) recommendations for the validation of a collecting and analysing method of DEHP in air, which will be used to quantify DEHP in air passing through PVC respiratory assistance MDs. The developed method met all the validation criteria for DEHP determination in air. DEHP in air passing through MDs on the sixth day reached a cumulative quantity of 122.86 µg when using a flow rate of 4 L min-1 of non-humidified air while it was of 49.22 µg; 58.12 µg and 29.61 µg with flow rates of 2 L min-1 of humidified air, 2 L min-1 of dry air and 4 L min-1 of humidified air, respectively. Model application to two patients undergoing two different respiratory procedure demonstrated that noninvasive ventilation patient received higher dose of inhaled DEHP, confirmed by DEHP metabolites quantification in urine. Although the protective effect of air humidifiers on DEHP exposure was demonstrated, the effect of flow rate is difficult to be established. This developed method should be tested to verify its capacity to collect and quantify other plasticizers used in PVC MDs.

How does continuous venovenous hemofiltration theoretically expose (ex-vivo models) inpatients to diethylhexyladipate, a plasticizer of PVC medical devices?

Continuous venovenous hemofiltration (CVVH) is widely used in intensive care units to treat patients with acute kidney injury requiring renal replacement therapy. The medical devices (MD) used for CVVH include a hemofilter and tubings made of plasticized PVC. Due to its known reprotoxicity, diethylhexyl phthalate (DEHP) has been replaced by alternatives such as diethylhexyladipate (DEHA) in some of these tubings. The migration of DEHA from hemofiltration systems has not been assessed and thus the level of patient exposure to this DEHP-alternative remains unknown. In this study, 2 CVVH models were used to evaluate the potential migration of DEHA from PVC tubings, allowing the determination of (Rachoin and Weisberg, 2019) the highest rates of DEHA able to migrate into a simulant flowing in a marketed adult CVVH circuit by disregarding any metabolisation and (Krieter et al., 2013) the clinical-reflecting exposure of patients to this plasticizer and its metabolites by assessing their migration into blood. In the first model, we showed that patients undergoing a CVVH procedure may be exposed to high rates of DEHA. Moreover, DEHA is continuously hydrolyzed into its primary metabolite MEHA (monoethylhexyladipate), which may reach cytotoxic level in the patients' blood. When looking from a « safer ¼ MD perspective, DEHA might not be the best alternative plasticizer for CVVH tubings. However, to reflect clinical conditions, this study should be completed by an in-vivo evaluation (biomonitoring) of the oxidized metabolites of DEHA in urines of inpatients undergoing CVVH.

Physicochemical Stability of Monoclonal Antibodies: A Review.

Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.

Compatibility of [99mTc]Tc-EDDA/HYNIC-TOC and [68Ga] Ga-DOTA-TOC in a syringe for intravenous administration.

OBJECTIVE: Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [Tc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [Ga]Ga-DOTA-TOC (Somakit-TOC). METHODS: Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (<25 ml). Sorption tests were performed according to the literature. RESULTS: After 2 h storage in a syringe, drug sorption of Tektrotyd and Somakit-TOC was of less than 2.5% and similar to other Tc-radiopharmaceuticals (range: from 1.1 ± 0.5% to 4.2 ± 0.6%). For Tektrotyd, this sorption phenomenon was positively influenced by the drug concentration and a short contact with the medical device (4.8 ± 0.2% up to 5 s vs. 2.3 ± 0.2%, n = 4; P < 0.001). For Somakit-TOC, the duration of contact with syringe had no impact (1.6 ± 0.2% up to 5 s vs. 1.7 ± 0.6%; P = 1.000). No drug radiolysis or alteration of microbiological aspects were observed. No impurity from a 3-piece-syringe was observed according to drug aspect, pH, and subvisible and visible particles, which remained within specification of the current European Pharmacopoeia. CONCLUSION: This study found that drug sorption to packaging was compatible with clinical use and absence of drug alteration of Tektrotyd and Somakit-TOC after repackaging in a syringe in polypropylene and prolonged storage during 2 h.