Entry of cannabidiol into the fetal, postnatal and adult rat brain.

Cannabidiol is a major component of cannabis but without known psychoactive properties. A wide range of properties have been attributed to it, such as anti-inflammatory, analgesic, anti-cancer, anti-seizure and anxiolytic. However, being a fairly new compound in its purified form, little is known about cannabidiol brain entry, especially during development. Sprague Dawley rats at four developmental ages: embryonic day E19, postnatal day P4 and P12 and non-pregnant adult females were administered intraperitoneal cannabidiol at 10 mg/kg with [3H] labelled cannabidiol. To investigate the extent of placental transfer, the drug was injected intravenously into E19 pregnant dams. Levels of [3H]-cannabidiol in blood plasma, cerebrospinal fluid and brain were estimated by liquid scintillation counting. Plasma protein binding of cannabidiol was identified by polyacrylamide gel electrophoresis and its bound and unbound fractions measured by ultrafiltration. Using available RNA-sequencing datasets of E19 rat brain, choroid plexus and placenta, as well as P5 and adult brain and choroid plexus, expression of 13 main cannabidiol receptors was analysed. Results showed that cannabidiol rapidly entered both the developing and adult brains. Entry into CSF was more limited. Its transfer across the placenta was substantially restricted as only about 50% of maternal blood plasma cannabidiol concentration was detected in fetal plasma. Albumin was the main, but not exclusive, cannabidiol binding protein at all ages. Several transcripts for cannabidiol receptors were expressed in age- and tissue-specific manner indicating that cannabidiol may have different functional effects in the fetal compared to adult brain.

Retrospective and FMECA analysis of failures in closed-system devices.

INTRODUCTION: Cytotoxic drugs can be hazardous to healthcare workers involved in their preparation and/or administration. Exposure occurs during routine handling of drug vials and ampoules, preparation, administration and disposal of cytotoxic waste. The use of closed-system devices provides protection against exposure to cytotoxics, but these devices are the subject of numerous incidents. Given the nature of the drugs they contain, these incidents can be dangerous for the personnel handling them. OBJECTIVE: The aim of our study is to analyze material vigilance data relating to problems frequently encountered with the various consumables of the closed system and to assess the risk of exposure of personnel to cytotoxic drugs when using these using the Failure Mode and Criticality Analysis (FMECA) method. MATERIALS AND METHODS: Our study was conducted at the pharmacy of the National Institute of Oncology, the closed system drug transfer device (CSDT) used is a ChemoClave-ICU®, This device is mechanical and needleless For the materiovigilance study we carried out a retrospective study over the period from 2019 to 2022, analyzing materiovigilance data collected by National Institute of Oncology's materiovigilance and pharmacovigilance cell. Our team, trained in the FMECA method, conducted the study over a three-month period, between September and November 2022. The method was used to assess the risks incurred by staff when using the CSDT device to prepare cytotoxic drugs. CONCLUSION: Our study revealed that the most frequent incident was linked to a manufacturing defect in the device in question. According to the FMECA analysis, this incident represents a major risk, as its occurrence hampers the cytotoxic preparation process. CSDT have the advantage of being easy to use and acceptable to staff, but standards need to be developed and validated to assess the performance of these devices.

Developing a flowchart to evaluate the use of Closed System Drug-Transfer Devices with monoclonal antibodies: Focus on the clinical trial setting.

OBJECTIVE: Available guidelines are ambiguous about safe handling monoclonal antibodies (MABs) and whether or not to use a Closed System Drug-Transfer Device (CSTD). In this article we want to describe a standardized working method on handling MABs in a clinical trial setting. DATA SOURCES: The current workflow at the clinical trial unit of the Ghent University Hospital was critically analyzed, after which an extensive literature review was performed using the National Institute for Occupational Safety and Health Working Group guidelines and the database PubMed (Keywords: monoclonal antibodies, closed system transfer devices, safety guidelines, safe handling, management, administration, (bio)compatibility, volume loss, contamination, clinical trial unit. Period: 2020-2022). DATA SUMMARY: Literature data are ambiguous. CSTDs can reduce cross-contamination and minimize exposure to potential hazardous drugs for healthcare professionals. However, in recent years more questions have been raised about their in-use compatibility and their impact on final product quality. This makes the debate on implementing CSTDs a hot topic in daily pharmacy practice and demands a holistic and standardized approach when deciding whether or not to use a CSTD when handling MABs. In a clinical trial setting, where safety data are frequently not available and the compatibility of CSTDs and investigational product is often unknown, this poses additional challenges that need to be taken into account. CONCLUSION: We developed a flowchart which standardizes the use of a CSTD when handling MABs. It allows other healthcare professionals and clinical trial sponsors to define and evaluate the necessary criteria when standardizing the position of a CSTD in their safe handling procedures.

Validation of chemotherapy drug vapor containment of an air cleaning closed-system drug transfer device.

PURPOSE: The purpose of this study was to test the efficacy of ChemfortTM, an air filtration closed-system drug transfer device to prevent release of chemotherapy drug vapors and aerosols under extreme conditions. The air cleaning system is based on the adsorption of drug vapors by an activated carbon filter in the Vial Adaptor before the air is released out of the drug vial. The functionality of the carbon filter was also tested at the end of device's shelf life, and after a contact period with drug vapors for 7 days. Cyclophosphamide and 5-fluorouracil were the chemotherapy drugs tested. METHODS: The Vial Adaptor was attached to a drug vial and both were placed in a glass vessel. A needle was punctured through the vessel stopper and the Vial Adaptor septum to allow nitrogen gas to flow into the vial and to exit the vial via the air filter into the glass vessel which was connected to a cold trap. Potential contaminated surfaces in the trap system were wiped or rinsed to collect the escaped drug. Samples were analyzed using liquid chromatography tandem mass spectrometry. RESULTS: Cyclophosphamide and 5-fluorouracil were detected on most surfaces inside the trap system for all Vial Adaptors without an activated carbon filter. Contamination did not differ between the Vial Adaptors with and without membrane filter indicating no effect of the membrane filter. The results show no release of either drug for the Vial Adaptors with an activated carbon filter even after 3 years of simulated aging and 7 days of exposure to drug vapors. CONCLUSIONS: Validation of air cleaning CSTDs is important to secure vapor and aerosol containment of chemotherapy and other hazardous drugs. The presented test method has proven to be appropriate for the validation of ChemfortTM Vial Adaptors. No release of cyclophosphamide and 5- fluorouracil was found even for Vial Adaptors after 3 years of simulated aging and 7 days of exposure to drug vapors.

Novel, vessel anatomy adjusting drug-coated balloon-Preclinical evaluation in peripheral porcine arteries.

BACKGROUND: The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB). METHODS: Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry. RESULTS: HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm2 vs. 3.26 ± 0.72 mm2 , p = .038) and area stenosis (OCT) was less (11.6 ± 6.9% vs. 24.7 ± 9.7%, p = .022). No premature death occurred and no in-life clinical symptoms or treatment-associated thrombi were observed. CONCLUSIONS: HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection.

Lactation during and after Breast Cancer.

Breastfeeding is an important aspect of mother-newborn relationship and is of great benefit for the baby. Unfortunately, many drugs taken by the mother may pass into her milk and exert an effect on the newborn. Very limited data is available and a cautionary approach is warranted especially when the woman receives anticancer treatment including chemotherapy , hormonal treatment and the recently introduced target agents as well as monoclonal antibodies. In all these conditions breastfeeding should be put on hold.More and more often physicians are faced with women that are pregnant years after the diagnosis of cancer: this has long been considered dangerous for the mother, but data show that prognosis is definitely not worse. If the woman is no longer being actively treated, breastfeeding is advisable every time it is possible, even if patients that received breast radiation may be unable to produce a sufficient amount of milk on that side.

Use of a closed-system drug transfer device reduces contamination with doxorubicin during bolus injection.

BACKGROUND: Administration of doxorubicin via bolus injection may result in environmental contamination and a risk of nurses becoming exposed. Small spills are frequently observed by nurses when syringes are connected to, and disconnected from, infusion lines. AIMS: The effect of a closed-system drug transfer device (CSTD) on the release of doxorubicin was studied during administration via bolus injections. METHODS: 10 administrations with the currently used technique and 10 administrations using the CSTD were compared by analysis of doxorubicin contamination on gauze pads, tissues and gloves. FINDINGS: Using the current technique, contamination was found during nine administrations, which was mainly on the gauze pads and, to a lesser extent, on the tissues and gloves, indicating release of doxorubicin during administration. With use of the CSTD, contamination was found only on one pair of gloves. CONCLUSION: Use of a CSTD significantly decreased the number of spills and level of contamination compared with the currently used technique and, consequently, the use of such devices offers a safer working environment for nurses.

Survey of guidelines and current practices for safe handling of antineoplastic and other hazardous drugs used in 24 countries.

PURPOSE: A survey of guidelines and current practices was conducted to examine the safe handling procedures for antineoplastic and other hazardous drugs that are used in 24 countries including the Americas, Europe, the Mideast, Far East, and Australia. METHODS: Subject experts were asked to complete a brief survey regarding safe handling guidelines and practices for hazardous drugs in their countries. Questions addressed practices for handling monoclonal antibodies, the use of closed-system transfer devices, medical surveillance practices, and measurements of compliance with existing guidelines. RESULTS: Responses from 37 subject experts representing 24 countries revealed considerable variation in the content and scope of safe handling guidelines and pharmacy practices among the participating countries. Guidelines in the majority of countries used the term "cytotoxics," while others referred to "hazardous" or "antineoplastic" drugs. The International Society of Oncology Pharmacy Practice standard was cited by six countries, and five cited the National Institute for Occupational Safety and Health Alert. Others cited international guidelines other than International Society of Oncology Pharmacy Practice, or they have created their own guidelines. Approximately half reported that their guidelines were mandatory under federal, state, or provincial legislation. Only 11 countries reported that monoclonal antibodies were covered in their guidelines. Closed-system drug-transfer devices are widely used, but were not specifically recommended in four countries, while one country required their use. Medical surveillance programs are in place in 20 countries, but only in The Netherlands is surveillance mandatory. Nine countries reported that they have completed recent updates or revisions of guidelines, and the measures for their adoption have been initiated. CONCLUSIONS: Although the overall goals in the participating countries were similar, the approaches taken to assure safe handling of hazardous drugs varied considerably in some cases.

Use and handling safety of Mini-Spike 2® chemo and puresite for safe chemotherapy compounding in a hospital pharmacy.

We wanted to evaluate the impact of Mini-Spike 2® Chemo + Puresite (MSCP) use on contamination surface levels, professionals' satisfaction and compounding time at pharmacy compared with Phaseal™. Presence of cyclophosphamide (CYP) and 5-fluorouracil (5FU) was evaluated at three sampling times: baseline; after a decontamination procedure and six months after MSCP use for CYP and 5FU compounding. Testing was carried out using an independent laboratory and wipe testing kit. To test compounding time, four different nurses followed the same compounding protocol with each device. We also developed a questionnaire to obtain feedback from the nurses. We did not find statistically significant differences in the median contamination surface levels between basal and final sampling time, CYP (0.140; 95% CI -1.135, 1.601), 5FU (-0.506; 95% CI -1.756, 0.287). We observed a difference of 10 s on compounding times between the two devices tested (p < 0.001) favoring MSCP. Finally, eight nurses answered the survey, with the best valued aspect as the aspiration/injection flow and resistance, and the worst value the comfort using Puresite and valve connection. MSCP maintains low surface contamination levels in our setting assuring compounding time standards. Satisfaction survey let us know which were the major advantages and disadvantages of the device.

Pre and post intervention study of antiblastic drugs contamination surface levels at a Pharmacy Department Compounding Area using a closed system drug transfer device and a decontamination process.

Assuring healthcare workers security on Hazardous Drugs (HD) compounding is critical in healthcare settings. Our study aims to demonstrate that the use of a Close System drug Transfer Device (CSTD) PhaSeal™ added to a decontamination process reduces antiblastic surface contamination levels in the Compounding Area (CA) of our Pharmacy Department (PD). We selected cyclophosphamide, 5-fluorouracil and iphosphamide to be evaluated. Testing was carried out with a wipe kit and quantified by an independent laboratory. We defined four sampling times: baseline; just after a decontamination procedure, which was repeated weekly during the study; four months after introduction of CSTD PhaSeal™ for cyclophosphamide and 5-fluorouracil compounding; and after eight months using CSTD PhaSeal™ for cyclophosphamide and 5-fluorouracil and one month for iphosphamide compounding. There was a decrease at the number of positive samples at the beginning/end of the study for all the drugs tested: 28/15 for cyclophosphide, 29/23 for iphosphamide and 7/1 for 5-fluorouracile. Comparing to the baseline, median cyclophosphamide levels significantly decreased (p-value <0.001) at 4 and 8 months sampling time (baseline: 1.01 ng/cm2 to 0.06 ng/cm2 and 0.01 ng/cm2), and median iphosphamide levels significantly decreased (p < 0.001) at 8 months sampling time (baseline: 3.02 ng/cm2 to 0.06 ng/cm2). 5-Fluorouracil did not show significant differences between the sampling times (baseline: 0.09 ng/cm2 to 0.09 ng/cm2). We saw a significant increase at iphosphamide levels at 4 months sampling point, contrary to cyclophosphamide, which levels had decreased. The use of CSTD PhaSeal™ for iphosphamide compounding the last month was implemented for ethical reasons after this intermediate results review. Our study suggests that the use of CSTD PhaSeal™, adding to decontaminating procedures, significantly reduces antiblastic drug surface levels at the CA of our PD.

Host pharmacokinetics and drug accumulation of anthelmintics within target helminth parasites of ruminants.

Anthelmintic drugs require effective concentrations to be attained at the site of parasite location for a certain period to assure their efficacy. The processes of absorption, distribution, metabolism and excretion (pharmacokinetic phase) directly influence drug concentrations attained at the site of action and the resultant pharmacological effect. The aim of the current review article was to provide an overview of the relationship between the pharmacokinetic features of different anthelmintic drugs, their availability in host tissues, accumulation within target helminths and resulting therapeutic efficacy. It focuses on the anthelmintics used in cattle and sheep for which published information on the overall topic is available; benzimidazoles, macrocyclic lactones and monepantel. Physicochemical properties, such as water solubility and dissolution rate, determine the ability of anthelmintic compounds to accumulate in the target parasites and consequently final clinical efficacy. The transcuticular absorption process is the main route of penetration for different drugs in nematodes and cestodes. However, oral ingestion is a main route of drug entry into adult liver flukes. Among other factors, the route of administration may substantially affect the pharmacokinetic behaviour of anthelmintic molecules and modify their efficacy. Oral administration improves drug efficacy against nematodes located in the gastroinestinal tract especially if parasites have a reduced susceptibility. Partitioning of the drug between gastrointestinal contents, mucosal tissue and the target parasite is important to enhance the drug exposure of the nematodes located in the lumen of the abomasum and/or small intestine. On the other hand, large inter-animal variability in drug exposure and subsequent high variability in efficacy is observed after topical administration of anthelmintic compounds. As it has been extensively demonstrated under experimental and field conditions, understanding pharmacokinetic behaviour and identification of different factors affecting drug activity is important for achieving optimal parasite control and avoiding selection for drug resistance. The search for novel alternatives to deliver enhanced drug concentrations within target helminth parasites may contribute to avoiding misuse, and prolong the lifespan of existing and novel anthelmintic compounds in the veterinary pharmaceutical market.

[In Vitro Evaluation Method for Drug Release and Particle Release from Drug Coated Balloon].

OBJECTIVES: Development in vitro test methods for drug release and particle release from drug coated balloon to address the disadvantages and inadequacy of existing assessment methods. METHODS: In vitro drug transfer test were carried out using the isolated porcine vessel as target site in the self-designed iliofemoral artery model, drug loss experiment during dilatation and retraction were added in drug release test, the particle test channel was subdivided and the size and number of the large particles were measured by microscopy combined with Image-Pro Plus software. RESULTS: The result shows that the method is feasible and the discrimination is good. The material balance can be achieved. More detailed data can be obtained. CONCLUSIONS: The developed in vitro evaluation method provides a reference for formulation screening, in vitro bench testing and in vivo pre-clinical animal testing.

Quantitative In Vitro Assessment of Liposome Stability and Drug Transfer Employing Asymmetrical Flow Field-Flow Fractionation (AF4).

PURPOSE: In the present study we introduce an efficient approach for a size-based separation of liposomes from plasma proteins employing AF4. We investigated vesicle stability and release behavior of the strongly lipophilic drug temoporfin from liposomes in human plasma for various incubation times at 37°C. METHODS: We used the radioactive tracer cholesteryl oleyl ether (COE) or dipalmitoyl-phosphocholine (DPPC) as lipid markers and (14)C-labeled temoporfin. First, both lipid labels were examined for their suitability as liposome markers. Furthermore, the influence of plasma origin on liposome stability and drug transfer was investigated. The effect of membrane fluidity and PEGylation on vesicle stability and drug release characteristics was also analyzed. RESULTS: Surprisingly, we observed an enzymatic transfer of (3)H-COE to lipoproteins due to the cholesterol ester transfer protein (CETP) in human plasma in dependence on membrane rigidity and were able to inhibit this transfer by plasma preincubation with the CETP inhibitor torcetrapib. This effect was not seen when liposomes were incubated in rat plasma. DPPC labels suffered from hydrolysis effects during preparation and/or storage. Fluid liposomes were less stable in human plasma than their PEGylated analogues or a rigid formulation. In contrast, the transfer of the incorporated drug to lipoproteins was higher for the rigid formulations. CONCLUSIONS: The observed effects render COE-labels questionable for in vivo studies using CEPT-rich species. Here, choline labelled (14)C-DPPC was found to be the most promising alternative. Bilayer composition has a high influence on stability and drug release of a liposomal formulation in human plasma.

Drug Release from ß-Cyclodextrin Complexes and Drug Transfer into Model Membranes Studied by Affinity Capillary Electrophoresis.

PURPOSE: Is to characterize the drug release from the ß-cyclodextrin (ß-CD) cavity and the drug transfer into model membranes by affinity capillary electrophoresis. Phospholipid liposomes with and without cholesterol were used to mimic the natural biological membrane. METHODS: The interaction of cationic and anionic drugs with ß-CD and the interaction of the drugs with liposomes were detected separately by measuring the drug mobility in ß-CD containing buffer and liposome containing buffer; respectively. Moreover, the kinetics of drug release from ß-CD and its transfer into liposomes with or without cholesterol was studied by investigation of changes in the migration behaviours of the drugs in samples, contained drug, ß-CD and liposome, at 1:1:1 molar ratio at different time intervals; zero time, 30 min, 1, 2, 4, 6, 8, 10 and 24 h. Lipophilic drugs such as propranolol and ibuprofen were chosen for this study, because they form complexes with ß-CD. RESULTS: The mobility of the both drug liposome mixtures changed with time to a final state. For samples of liposomal membranes with cholesterol the final state was faster reached than without cholesterol. CONCLUSIONS: The study confirmed that the drug release from the CD cavity and its transfer into the model membrane was more enhanced by the competitive displacement of the drug from the ß-CD cavity by cholesterol, the membrane component. The ACE method here developed can be used to optimize the drug release from CD complexes and the drug transfer into model membranes.

Evaluation of a closed-system cytotoxic transfer device in a pharmaceutical isolator.

PURPOSE: The occupational risk associated with handling of cytotoxic anticancer drugs is well documented and, in many countries, pharmaceutical isolators are used to contain cytotoxic residues during preparation of cytotoxic infusions. Isolators are difficult to clean leading to concerns that cytotoxic contamination from the work area could be transferred to surfaces of products leaving the isolator. This study investigated the surface contamination arising from the preparation of five anticancer drug infusions (Epirubicin, Fluorouracil, Cisplatin, Oxaliplatin and Carboplatin) in a pharmaceutical isolator and compared use of a conventional syringe and needle technique with a closed-system drug transfer device (CSDTD). METHODS: Wipe samples were taken over 1 week from pre-defined areas in the isolator, gloves, preparation mats, and also from the surfaces of prepared cytotoxic infusion bags and pre-filled syringes to obtain baseline surface contamination data. Following operator familiarisation, the CSDTD was then introduced and sampling repeated for a further week (intervention period). The samples obtained were analysed using validated HPLC-UV, HPLC-FL and ICP-MS techniques, as appropriate. RESULTS: All surfaces sampled during baseline, including external surfaces of infusions and syringes, were contaminated with each marker drug. During the intervention phase, isolator surfaces were free from detectable contamination and the contamination measured on gloves, preparation mats and surface of infusions was markedly reduced. The frequency of contamination on syringe and infusion surfaces was also lower. CONCLUSION: Surface contamination from cytotoxic infusion preparation in a pharmaceutical isolator was significant and could transmit cytotoxic residues to patient and public areas via infusion surfaces. The frequency and amount of contamination were reduced by the CSDTD.

Perianesthetic Considerations for the Breastfeeding Mother.

Breastfeeding has been shown to be beneficial in the development of infants, but sometimes, the breastfeeding mother may require anesthesia. It is important for perianesthesia caregivers to understand how the breastfed infant may be affected by the anesthetic medications received by the breastfeeding mother. This article reviews current literature on drug transfer into breast milk and specifically how anesthetic drugs may affect breastfed infants. The pharmacokinetics of drug transfer during lactation is described as well as considerations for perianesthesia providers when caring for breastfeeding patients. The results of this literature review provide evidence that there is little risk to the breastfed infant after the mother receives surgical anesthesia. However, the type of drug, the dosage, the timing of treatment, and the infant's age and health must be taken into consideration.

Investigations on the transfer of porphyrin from o/w emulsion droplets to liposomes with two different methods.

CONTEXT: Due to their small particle size, colloidal fat emulsions are suitable for intravenous administration. In order to obtain information on their potential in vivo performance, it is important to find a simple and effective in vitro assay to evaluate the drug release behavior of such particles. OBJECTIVE: Two in vitro methods were studied to measure the transfer of a lipophilic model drug from colloidal o/w emulsion droplets (donor) to liposomes (acceptor), which serve as model membranes mimicking cell membranes in the body. In the first method (column method) the acceptor particles were neutral unilamellar vesicles. In the second method (MLV method), multilamellar vesicles (MLV) were used as acceptor. MATERIALS AND METHODS: The donor nanoemulsions were prepared by high pressure homogenization. Z-average particle size, polydispersity index and zeta potential were determined. RESULTS: The transfer of porphyrin was moderate to the acceptor MLV and rapid to the acceptor unilamellar vesicles. The amount of transferred porphyrin at the end of the experiment depended on the transfer method and the donor/acceptor ratio. With both acceptors the transfer of porphyrin stopped at a concentration lower than the theoretical equilibrium values. DISCUSSION: Many factors such as acceptor particle size and donor to acceptor lipid molar ratio affect the drug transfer from the donor particles to the different acceptors. CONCLUSION: Both methods seem to be suitable to study the drug transfer from such colloidal emulsion and the use of lipophilic acceptor particles is a better approach to the conditions in blood.

Occupational exposure to anti-cancer drugs: A review of effects of new technology.

Because anti-cancer drugs are non-selective, they affect both cancerous and non-cancerous cells. Being carcinogenic and mutagenic, many anticancer drugs therefore present a major health risk to healthcare staff working with them. This paper reviews the means by which exposure to anti-cancer drugs in the workplace may be monitored, assessed and reduced. Both biological monitoring, using non-selective methods or compound-selective methods, and environmental monitoring have provided information on the nature and degree of exposure in the workplace. Pharmaceutical isolators, used for the compounding of cytotoxic IV infusions and the preparation of injectable drugs, provide a physical barrier between pharmacists and cytotoxic drugs and reduce direct exposure. However, the interior of isolators and the contents thereof (e.g. infusion bags and syringes) are readily contaminated by aerosols and spillages and afford a secondary source of exposure to pharmacists, nurses and cleaning staff. Closed system transfer devices (CSTDs), designed to prohibit the transfer of contaminants into the working environment during drug transfer between the vial and syringe, have been successful in further reducing, but not eliminating surface contamination. Given that the number of patients requiring treatment with chemotherapeutic agents is predicted to increase, further efforts to reduce occupational exposure to anti-cancer drugs, including the refinement and wider use of CTSDs, are recommended.

Drug transfer during intimate moments: A key issue in doping control that can be documented by hair tests of the athlete and the partner.

The presence of a prohibited substance or its metabolites or its markers in an athlete's sample constitutes the more frequent anti-doping rules violation. In the world anti-doping code, it is indicated (point 10.5) that if someone establishes in an individual case that the athlete bears no fault or negligence, then the otherwise applicable period of ineligibility shall be eliminated. The conditions that have to be met to fix the no fault or negligence evidence are described in several other points of the code. The following two points are of paramount importance: 1. the athlete or his/her legal representative must present verified circumstances of contamination and the source of contamination must be identified; and 2. there must be verified claims by the athlete about the fact that he/she did not knowingly take the prohibited substance, i.e., that the violation was not intentional.In recent years, several cases of contamination involving drug transfer during intimate moments have been reported. This later situation was first reported in 2009 with the Richard Gasquet case. Since that time, several athletes have been allowed to return to competition with no charge based on strong evidence that the source of contamination was drug transfer during intimate moments. As some of these cases are public and because the author performed hair tests for the majority of the international athletes involved in such procedures, the strategy of the defence and the scientific bases of discussion are reviewed in this article.

Evidence of ostarine cross-contamination via sweat in 2 athletes sharing the same neoprene hamstring sleeves. An original situation of drug transfer where the anti-doping rule violation was suspended by the sport authorities.

The presence of ostarine, a selective androgen receptor modulator (SARM) in an athlete's sample constitutes one of the most frequent anti-doping rules violation. It is possible to challenge this violation but it is the athlete who has to demonstrate he / she is innocent. The conditions to evidence no fault or negligence are mostly based on 2 points: 1. the athlete or his/her legal representative must present verified circumstances of contamination and the source of contamination must be identified; and 2. there must be verified claims by the athlete about the fact that he / she did not knowingly take the prohibited substance, i.e. that the violation was not intentional. During a 2-weeks period, a male athlete tested two times positive for ostarine in urine (<0.1 ng/ml) and he challenged these results. His hair and nail tests returned negative (LOQ at 0.5 pg/mg). He admitted using two neoprene hamstring sleeves of another athlete who confessed abusing ostarine. This was confirmed in his hair (190 pg/mg), his fingernail clippings (780 pg/mg) and his toenail clippings (45 pg/mg). To document the presence of ostarine in the hamstring sleeves and therefore possible drug transfer, the hamstring sleeves were analysed. Ostarine was identified in 12 different selected pieces (about 1 g) of the sleeves at concentrations ranging from 3 to 142 pg/g. Sport authorities (USADA) agreed that the most likely source of contamination was the hamstring sleeves, thus confirming the scenario of drug transfer and gave the athlete a no fault.