Assessment of the surface contamination of the primary packaging of oral antineoplastic drugs and secondary packaging of chemotherapy preparations at a Swiss hospital.

INTRODUCTION: Due to the high toxicity of antineoplastic drugs, handling their packaging could lead to the chemical contamination of hospital environments and exposure risks to healthcare professionals and patients. This study aimed to assess the contamination of two main surfaces: the outer primary packaging of oral antineoplastic drug formulations (n = 36) available on the Swiss market and the surface of secondary packaging of injectable antineoplastic drug preparations (n = 60) produced by the pharmacy of a Swiss hospital and carriers used for transport (n = 5). METHODS: Samples were collected using a validated wipe sampling method. The simultaneous analysis of 24 antineoplastic drugs: 5-fluorouracil, busulfan, carboplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine, vincristine) and 1 antiviral compound (ganciclovir) was performed by UHPLC-MS/MS. RESULTS: A total of 58% and 90% positive results were obtained for the primary packaging of oral chemotherapies and for the secondary packaging of injectable preparations, respectively. The highest quantities found on the primary packaging for oral chemotherapies and on the surface of closed leak-proof bags were 111 ng of methotrexate and 19 ng of gemcitabine, respectively. Gemcitabine (69%) and cyclophosphamide (38%) were the two most common contaminants found on the packaging of injectable preparations and carriers, regardless of the chemotherapy preparations. CONCLUSION: Trace levels (ng) of antineoplastic drugs can be found on most surfaces of all evaluated pharmaceutical products. Thus, suitable personal protective equipment is mandatory for healthcare professional handling antineoplastic drugs.

Efficiency of degradation or desorption methods in antineoplastic drug decontamination: A critical review.

Although considerable efforts have been made over the last 40 years, occupational exposure to antineoplastic drugs is still a daily concern, since eradicating such contamination from workplaces seems unattainable. Considerable data are currently available on the risks associated with their use at work. Hospital facilities are often cleaned with marketed antimicrobials whose chemical decontamination efficacy certainly differs but remains unknown. To keep compounding facilities sterile, alcohol-based solutions are frequently used but with very limited efficiency. It would be particularly useful if a decontamination method could be added to the means already available so that all conventional antineoplastic drug contamination could be removed. Several degradation methods or desorption methods have previously been experimented, with varying success. They have never been compared or discussed in terms either of efficiency or usability. This review aims to analyse and discuss the results of each degradation or decontamination procedure and to compare them. This should facilitate selection of the method to be implemented in daily practice.

Determination of 16 antineoplastic drugs by capillary electrophoresis with UV detection: Applications in quality control.

Two capillary electrophoresis (CE) methods were developed for the analysis of 16 antineoplastic drugs contained in injectable pharmaceutical formulations. A capillary zone electrophoresis (CZE) method coupled to UV was developed with a background electrolyte (BGE) made of a 100 mM phosphate buffer at pH 2.5 containing 50% v/v of acetonitrile and dynamic coating of capillaries with Ceofix®. This method allowed the analysis of doxorubicin, epirubicin, idarubicin, daunorubicin, irinotecan, topotecan, vincristine, vindesine, vinblastine, and vinorelbine in less than 8 min. A micellar electrokinetic chromatography (MEKC) method coupled to UV was also developed for the determination of methotrexate, pemetrexed, etoposide, etoposide phosphate, fludarabine phosphate, and 5-fluorouracil. A run time of 16 min was obtained with a BGE made of 50 mM borate buffer at pH 9.2 with 80 mM of sodium dodecyl sulfate (SDS) and 20% v/v of acetonitrile. For both methods, the applied voltage was 30 kV and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in fused silica capillaries with an internal diameter of 50 µm and a total length of 64.5 cm. Both methods were validated and trueness values between 99.4 and 101.3% were obtained with repeatability and intermediate precision values of 0.5-1.8% for all drugs. These methods were found appropriate for controlling injectable pharmaceutical formulations containing antineoplastic drugs and successfully applied in quality control.

Antineoplastic drugs and their analysis: a state of the art review.

The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

Long-term stability of ganciclovir in polypropylene containers at room temperature.

Purpose Ganciclovir is increasingly provided by hospital pharmacy production unit in a ready-to-use form, in order to improve the safety of healthcare workers and the efficiency of the organisation. The objective of this study was to develop a stability-indicating method to assay ganciclovir and determine the stability of ganciclovir in syringes (5 mg/mL) and infusion bags (0.25 and 5 mg/mL) at two different temperatures. Method Ganciclovir solutions (0.25 mg/mL and 5 mg/mL) in 0.9% sodium chloride were prepared in 50 mL polypropylene syringes or 100 mL polypropylene infusion bags and stored at 2-8℃ and 23-27℃. The chemical stability was measured using a stability-indicating Ultra High Performance Liquid Chromatography coupled to mass spectrometry method. Physical stability was assessed by visual inspection. Results No significant loss of ganciclovir under any of the tested conditions was observed in this study. All solutions remained clear through the study period. Conclusion All tested formulations remained stable for at least 185 days independently of container type, temperature or concentration studied.

Reliability of chemotherapy preparation processes: Evaluating independent double-checking and computer-assisted gravimetric control.

Background and objectives Centralized chemotherapy preparation units have established systematic strategies to avoid errors. Our work aimed to evaluate the accuracy of manual preparations associated with different control methods. Method A simulation study in an operational setting used phenylephrine and lidocaine as markers. Each operator prepared syringes that were controlled using a different method during each of three sessions (no control, visual double-checking, and gravimetric control). Eight reconstitutions and dilutions were prepared in each session, with variable doses and volumes, using different concentrations of stock solutions. Results were analyzed according to qualitative (choice of stock solution) and quantitative criteria (accurate, <5% deviation from the target concentration; weakly accurate, 5%-10%; inaccurate, 10%-30%; wrong, >30% deviation). Results Eleven operators carried out 19 sessions. No final preparation (n = 438) contained a wrong drug. The protocol involving no control failed to detect 1 of 3 dose errors made and double-checking failed to detect 3 of 7 dose errors. The gravimetric control method detected all 5 out of 5 dose errors. The accuracy of the doses measured was equivalent across the control methods ( p = 0.63 Kruskal-Wallis). The final preparations ranged from 58% to 60% accurate, 25% to 27% weakly accurate, 14% to 17% inaccurate and 0.9% wrong. A high variability was observed between operators. Discussion Gravimetric control was the only method able to detect all dose errors, but it did not improve dose accuracy. A dose accuracy with <5% deviation cannot always be guaranteed using manual production. Automation should be considered in the future.

Efficacy of Two Cleaning Solutions for the Decontamination of 10 Antineoplastic Agents in the Biosafety Cabinets of a Hospital Pharmacy.

OBJECTIVE: This study aimed to evaluate two cleaning solutions for the chemical decontamination of antineoplastic agents on the surfaces of two biosafety cabinets routinely used for chemotherapy preparation in a hospital pharmacy. METHODS: For almost 1 year (49 weeks), two different solutions were used for the weekly cleaning of two biosafety cabinets in a hospital pharmacy's centralized cytotoxic preparation unit. The solutions evaluated were a commercial solution of isopropyl alcohol (IPA) and water (70:30, vol:vol), and a detergent solution constituted by 10(-2)M of sodium dodecyl sulfate (SDS) with 20% IPA. Seven areas in each biosafety cabinet were wiped 14 times throughout the year, before and after the weekly cleaning process, according to a validated procedure. Samples were analyzed using a validated method of high-performance liquid chromatography coupled to mass spectrometry. The decontamination efficacy of these two solutions was tested for 10 antineoplastic agents: cytarabine, gemcitabine, methotrexate, etoposide phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin, epirubicin, and vincristine. RESULTS: Overall decontamination efficacies observed were 82±6% and 49±11% for SDS solution and IPA, respectively. Higher contamination levels were distributed on areas frequently touched by the pharmacy technicians-such as sleeves and airlock handles-than on scale plates, gravimetric control hardware, and work benches. Detected contaminations of cyclophosphamide, ifosfamide, gemcitabine, and cytarabine were higher than those of the others agents. SDS solution was almost 20% more efficient than IPA on eight of the antineoplastic agents. CONCLUSION: Both cleaning solutions were able to reduce contamination levels in the biosafety cabinets. The efficacy of the solution containing an anionic detergent agent (SDS) was shown to be generally higher than that of IPA and, after the SDS cleaning procedure, biosafety cabinets demonstrated acceptable contamination levels.

Prioritization methodology for the monitoring of active pharmaceutical ingredients in hospital effluents.

The important number of active pharmaceutical ingredients (API) available on the market along with their potential adverse effects in the aquatic ecosystems, lead to the development of prioritization methods, which allow choosing priority molecules to monitor based on a set of selected criteria. Due to the large volumes of API used in hospitals, an increasing attention has been recently paid to their effluents as a source of environmental pollution. Based on the consumption data of a Swiss university hospital, about hundred of API has been prioritized following an OPBT approach (Occurrence, Persistence, Bioaccumulation and Toxicity). In addition, an Environmental Risk Assessment (ERA) allowed prioritizing API based on predicted concentrations and environmental toxicity data found in the literature for 71 compounds. Both prioritization approaches were compared. OPBT prioritization results highlight the high concern of some non steroidal anti-inflammatory drugs and antiviral drugs, whereas antibiotics are revealed by ERA as potentially problematic to the aquatic ecosystems. Nevertheless, according to the predicted risk quotient, only the hospital fraction of ciprofloxacin represents a risk to the aquatic organisms. Some compounds were highlighted as high-priority with both methods: ibuprofen, trimethoprim, sulfamethoxazole, ritonavir, gabapentin, amoxicillin, ciprofloxacin, raltegravir, propofol, etc. Analyzing consumption data and building prioritization lists helped choosing about 15 API to be monitored in hospital wastewaters. The API ranking approach adopted in this study can be easily transposed to any other hospitals, which have the will to look at the contamination of their effluents.

Development of an LC-MS/MS Method for the Assessment of Selected Active Pharmaceuticals and Metabolites in Wastewaters of a Swiss University Hospital.

A multi-residue analytical method was developed and validated for the quantification of 11 selected active pharmaceutical ingredients (API) and 2 human metabolites in hospital effluents using solid-phase extraction followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Targeted analytes belong to different therapeutic classes: non steroidal anti-inflammatory drugs (NSAID), analgesics, antibiotics and psychiatric drugs. Solid-phase extraction recoveries ranged between 21 and 101% for the selected API. Calibration curves were built with 6 standard samples prepared in ultrapure water ranging from 0.05 to 10 µg/L and showed regression coefficients above 0.994. The instrumental detection limits (IDL) varied between 0.05 and 5 µg/L, and the method detection limits (MDL) between 0.1 and 100 ng/L. Precision of the method, evaluated with spiked water samples at four different concentrations, varied between 84 and 117% for all compounds and an overall variability below 20%, with the exception of carbamazepine (71-123%). Except for two compounds, recoveries of spiked hospital wastewaters at four different concentrations (0.1, 1, 10 and 100 µg/L) varied between 44 and 133%, with relative standard deviation (RSD) between 0.6 and 28.5%. The evaluation of the matrix effects showed that diluted samples exhibit lower signal suppression. Analysis of effluent samples from a Swiss university hospital resulted in a mean detection frequency of 92% for the selected compounds, with concentrations up to 1535 µg/L for the analgesic paracetamol.

Determination of the external contamination and cross-contamination by cytotoxic drugs on the surfaces of vials available on the Swiss market.

INTRODUCTION: The external contamination and cross-contamination by cytotoxic drugs on the surface (outside and septum) of 133 vials from various manufacturers and available on the Swiss market were evaluated. All of the tested vials contained one of the following active ingredients: cyclophosphamide, cytarabine, doxorubicin, epirubicin, etoposide phosphate, gemcitabine, ifosfamide, irinotecan, methotrexate or vincristine. METHODS AND MATERIALS: The validated wiping liquid chromatography-mass spectrometry method used in this study allowed for the simultaneous determination of these 10 cytotoxic drugs in less than 30 min. RESULTS: External contamination by cytotoxic drugs was detected on 63% of tested vials (outside and septum). The highest contamination level was observed on etoposide phosphate vials with 1896.66 ng of active ingredient on the outside of the vial. Approximately 20% of the contaminated vials had greater than 10 ng of cytotoxic drugs. Chemical contamination on the septum was detected on 38% of the vials. No contamination or very low levels of cytotoxic drugs, less than 1 ng per vial, were detected on the vials protected by plastic shrink-wrap. Traces of cytotoxic drugs different from the active ingredient were detected on 35% of the tested vials. CONCLUSION: Handling cytotoxic vials with gloves and having a procedure for the decontamination of vials are of the utmost importance for reducing exposure to cytotoxic drugs. Moreover, manufacturers must improve their procedures to provide products free from any contamination.

Evaluation of decontamination efficacy of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents.

OBJECTIVES: The handling of antineoplastic agents results in chronic surface contamination that must be minimized and eliminated. This study was designed to assess the potential of several chemical solutions to decontaminate two types of work surfaces that were intentionally contaminated with antineoplastic drugs. METHODS: A range of solutions with variable physicochemical properties such as their hydrophilic/hydrophobic balance, oxidizing power, desorption, and solubilization were tested: ultrapure water, isopropyl alcohol, acetone, sodium hypochlorite, and surfactants such as dishwashing liquid (DWL), sodium dodecyl sulfate (SDS), Tween 40, and Span 80. These solutions were tested on 10 antineoplastic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin, epirubicin, and vincristine. To simulate contaminated surfaces, these molecules (200ng) were deliberately spread onto two types of work surfaces: stainless steel and glass. Recovered by wiping with a specific aqueous solvent (acetonitrile/HCOOH; 20/0.1%) and an absorbent wipe (Whatman 903®), the residual contamination was quantified using high-performance liquid chromatography (HPLC) coupled to mass spectrometry. To compare all tested cleaning solutions, a performance value of effectiveness was determined from contamination residues of the 10 drugs. RESULTS: Sodium hypochlorite showed the highest overall effectiveness with 98% contamination removed. Ultrapure water, isopropyl alcohol/water, and acetone were less effective with effectiveness values of 76.8, 80.7, and 40.4%, respectively. Ultrapure water was effective on most hydrophilic molecules (97.1% for cytarabine), while on the other hand, isopropyl alcohol/water (70/30, vol/vol) was effective on the least hydrophilic ones (85.2% for doxorubicin and 87.8% for epirubicin). Acetone had little effect, whatever the type of molecule. Among products containing surfactants, DWL was found effective (91.5%), but its formulation was unknown. Formulations with single surfactant non-ionics (tween 40 and span 80) or anionic (SDS) were also tested. Finally, solutions containing 10(-2) M anionic surfactants and 20% isopropyl alcohol had the highest global effectiveness at around 90%. More precisely, their efficacy was the highest (94.8%) for the most hydrophilic compounds such as cytarabine and around 80.0% for anthracyclines. Finally, the addition of isopropyl alcohol to surfactant solutions enhanced their decontamination efficiency on the least hydrophilic molecules. Measured values from the stainless steel surface were similar to those from the glass one. CONCLUSION: This study demonstrates that all decontamination agents reduce antineoplastic contamination on work surfaces, but none removes it totally. Although very effective, sodium hypochlorite cannot be used routinely on stainless steel surfaces. Solutions containing anionic surfactant such as SDS, with a high efficiency/safety ratio, proved most promising in terms of surface decontamination.

Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces.

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm(-2)) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Development and Proof of Concept of an Audit Toolkit for the Safe Handling of Cytotoxic Drugs in Low- and Middle-Income Countries.

PURPOSE: Chemotherapies are considered high-risk drugs for patient and staff safety. Considering the rising burden of cancer and the increasing use of chemotherapy drugs in low- and middle-income countries (LMICs), promoting continuous improvements in the safety and quality of practices in these settings is essential. This paper describes the development and proof of concept of a toolkit to audit chemotherapy handling practices in the health care facilities of LMICs. METHODS: A steering committee defined the audit method and the toolkit content. Several checklists were developed to facilitate the audit and data collection. Items included in checklists were derived from key reference works on safe handling. Different tools were validated using Delphi surveys and expert reviews. Audits of pilot sites were performed to test the toolkit's applicability and relevance. RESULTS: The toolkit contains a 134-item global assessment tool for the different processes at each step of the medication pathway and three step-specific observation checklists to assess different health workers' practices during the prescription, preparation, and administration of chemotherapies. The toolkit also proposes using a surface-wipe sampling method to measure any cytotoxic contamination of the immediate environment. The toolkit was tested in three teaching hospitals in Africa. CONCLUSION: The toolkit developed was successfully implemented in a variety of LMIC settings, providing a comprehensive evaluation of the quality and safety of the chemotherapy drug handling practices in participating health care facilities. This toolkit can help facilities in LMICs to implement a new approach to continuously improving the quality and safety of their practices and ultimately ensure patient and staff safety.

Wipe-sampling procedure optimisation for the determination of 23 antineoplastic drugs used in the hospital pharmacy.

PURPOSE: Optimise a wipe sampling procedure to evaluate the surface contamination for 23 antineoplastic drugs used in the hospital pharmacy. METHODS: The influence of various parameters (ie, sampling device, sampling solution, desorption modes) was evaluated using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method able to quantify 23 antineoplastic drugs widely used in the hospital pharmacy: 5-fluorouracil, busulfan, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, etoposide phosphate, fludarabine phosphate, ganciclovir, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, paclitaxel, pemetrexed, raltitrexed, topotecan and vincristine. Best conditions were tested with real samples from a hospital pharmacy chemotherapy compounding unit. RESULTS: Polyester swabs (TX714 and TX716) gave satisfactory results for the desorption step for all compounds with mean recoveries of 90% and 95%, respectively. For the wiping step, higher recoveries were obtained using TX716 and isopropanol 75% as wiping solution. As anticipated, most intense contaminations were found close to the chemotherapy production site, on surfaces the most frequently in contact with operators' hands. CONCLUSION: Wipe sampling method was successfully developed and applied to real samples to determine surface contamination with 23 antineoplastic agents in trace amounts.

Simultaneous quantification of ten cytotoxic drugs by a validated LC-ESI-MS/MS method.

A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21 min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2 ng mL(-1) for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces.

Efficiency of four solutions in removing 23 conventional antineoplastic drugs from contaminated surfaces.

BACKGROUND: Residual contamination by intravenous conventional antineoplastic drugs (ICAD) is still a daily issue in hospital facilities. This study aimed to compare the efficiency (EffQ) of 4 different solutions to remove 23 widely used ICADs from surfaces. METHOD AND FINDINGS: A solution containing 23 ICADs (4 alkylating agents, 8 antimetabolites, 2 topo-I inhibitors, 6 topo-II inhibitors and 3 spindle poisons) was spread over 100 cm2 stainless steel. After drying, decontamination was carried out using 10×10 cm wipes moistened with 300 µL of one of the following solutions: 70% isopropanol (S1); ethanol-hydrogen peroxide 91.6-50.0 mg/g (S2); 10-2 M sodium dodecyl sulphate/isopropanol 80/20 (S3) or 0.5% sodium hypochlorite (S4). Six tests were performed for each decontamination solution. Two modalities were tested: a single wipe motion from top to bottom or vigorous wiping (n = 6 for each modality). Residual contamination was measured with a validated liquid chromatography with tandem mass spectrometry detection method. Solution efficiency (in %) was computed as follows: EffQ = 1-(quantity after decontamination/quantity before decontamination), as median (min-max) for the 23 ICADs. The overall decontamination efficiency (EffQ) of the 4 solutions was compared by a Kruskall-Wallis test. Decontamination modalities were compared for each solution and per ICAD with a Mann-Whitney test (p<0.05). EffQ were significantly different from one solution to the next for single wipe motion decontamination: 79.9% (69.3-100), 86.5% (13.0-100), 85.4% (56.5-100) and 100% (52.9-100) for S1, S2, S3 and S4 (p<0.0001), respectively. Differences were also significant for vigorous decontamination: EffQ of 84.3% (66.0-100), 92.3% (68.7-100), 99.6% (84.8-100) and 100% (82.9-100) for S1, S2, S3 and S4, respectively (p<0.0001). Generally, vigorous decontamination increased EffQ for all tested solutions and more significantly for the surfactant. CONCLUSION: Decontamination efficiency depended on the solution used but also on the application modality. An SDS admixture seems to be a good alternative to sodium hypochlorite, notably after vigorous chemical decontamination with no hazard either to materials or workers.

Chemical Decontamination of Hazardous Drugs: A Comparison of Solution Performances.

OBJECTIVES: Over the past 40 years, numerous actions have been undertaken to decrease the contamination of hospital facilities by intravenous conventional antineoplastic drugs (ICADs) such as centralizing compounding in pharmacies, using personal protective equipment, specific compounding, or infusion devices. As recently proposed in the monograph, an additional specific decontamination step must be envisaged. A recent literature review analysed and discussed the different solutions tested in terms of decontamination efficacy. This article aims to discuss the performance of these solutions in the framework of aseptic compounding. METHODS: The same dataset used in the previous literature review was reanalysed according to other parameters so as to select decontamination solutions: overall decontamination efficiency (EffQ), tested contaminants, and the risks of use in daily practice. RESULTS: Using an EffQ threshold of 90% resulted in discarding 26 out of the 59 solutions. Solutions were tested differently: 8 on 1 contaminant, 11 on 2 contaminants, and 14 solutions on between 3 and 11 contaminants. Three risks were identified to help make choices in routine practice: the mutagenicity of degradation products, the safety of operators and facilities, and respect for the aseptic environment. CONCLUSIONS: From the results, performance is discussed according to specific situations: a one-time incident or the basic chemical contamination due to daily practice. Accordingly, the decontamination solution selected then required a risk analysis and an evaluation before implementing it in the daily practice of a compounding unit.

Determination of suxamethonium in a pharmaceutical formulation by capillary electrophoresis with contactless conductivity detection (CE-C(4)D).

A simple method based on capillary electrophoresis with a capacitively coupled contactless conductivity detector (CE-C(4)D) was developed for the determination of suxamethonium (SUX) in a pharmaceutical formulation. A hydro-organic mixture, consisting of 100mM Tris-acetate buffer at pH 4.2 and acetonitrile (90:10, v/v), was selected as background electrolyte (BGE). The applied voltage was 30kV, and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in a fused silica capillary with an internal diameter of 50 microm and a total length of 64.5cm. Under these conditions, a complete separation between SUX, sodium ions and the main degradation products (choline) was achieved in less than 4min. The presence of acetonitrile in the BGE allowed a reduction of SUX adsorption on the capillary wall. The CE-C(4)D method was validated, and trueness values between 98.8% and 101.1% were obtained with repeatability and intermediate precision values of 0.7-1.3% and 1.2-1.6%, respectively. Therefore, this method was found appropriate for controlling pharmaceutical formulations containing suxamethonium and degradation products.

Validation and uncertainty estimation for trace amounts determination of 25 drugs used in hospital chemotherapy compounding units.

The validation and uncertainty assessment of the analytical method developed for the simultaneous determination of 25 anticancer drugs commonly handled in hospital pharmacy was reported. Selected compounds were 5-fluorouracil, cytarabine, fludarabine phosphate, ganciclovir, gemcitabine, dacarbazine, methotrexate, pemetrexed, busulfan, raltitrexed, etoposide phosphate, topotecan, ifosfamide, cyclophosphamide, irinotecan, doxorubicin, epirubicin, daunorubicin, idarubicin, vincristine, vinblastine, vinorelbine, docetaxel and paclitaxel. Accuracy and uncertainty profiles were obtained for all compounds. Quantitative performances were satisfactory in term of specificity, sensitivity, precision and accuracy. Repeatability (1.9-25.4%) and intermediate precision (2.7-29%) were determined for all target compounds. Lower limits of quantification between 1 and 25 ng/mL were obtained. Uncertainty associated to measurement of routine samples was evaluated. The multi-targeted method was specific and reliable and was successfully applied to wipe samples from hospital pharmacy chemotherapy compounding unit and to the determination of outside contamination of vials from pharmaceutical manufacturers.

[Biosimilar monoclonal antibodies: comparative study of analytical and functional quality]. / Anticorps monoclonaux biosimilaires - Étude comparative des qualités analytique et fonctionnelle.

Biosimilars marketing authorization requires a strict demonstration of similarity with the reference antibody, through preclinical and clinical studies. This article reviews the panel of in vitro physicochemical and functional analyses, which are performed prior to clinical studies. For each critical attribute of the antibody, we detail the commonly used analytical techniques, their working principle and the type of information they may give.

TITLE: Anticorps monoclonaux biosimilaires - Étude comparative des qualités analytique et fonctionnelle. ABSTRACT: La mise sur le marché de biosimilaires requiert une démonstration stricte de la similarité avec l'anticorps de référence, au travers d'études précliniques et cliniques. Cet article synthétise l'ensemble des analyses physicochimiques et fonctionnelles mises en œuvre in vitro, préalables à la réalisation d'études cliniques. Pour chaque caractéristique critique de l'anticorps, nous avons détaillé les techniques analytiques communément employées, leur principe de fonctionnement, ainsi que le type d'informations que ces techniques permettent d'obtenir.