Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part II - the application of the FMECA method to compare manual vs automated preparation.

Healthcare workers handling antineoplastic drugs (ADs) in preparation units run the risk of occupational exposure to contaminated surfaces and associated mutagenic, teratogenic, and oncogenic effects of those drugs. To minimise this risk, automated compounding systems, mainly robots, have been replacing manual preparation of intravenous drugs for the last 20 years now, and their number is on the rise. To evaluate contamination risk and the quality of the working environment for healthcare workers preparing ADs, we applied the Failure Mode Effects and Criticality Analysis (FMECA) method to compare the acceptable risk level (ARL), based on the risk priority number (RPN) calculated from five identified failure modes, with the measured risk level (MRL). The model has shown higher risk of exposure with powdered ADs and containers not protected by external plastic shrink film, but we found no clear difference in contamination risk between manual and automated preparation. This approach could be useful to assess and prevent the risk of occupational exposure for healthcare workers coming from residual cytotoxic contamination both for current handling procedures and the newly designed ones. At the same time, contamination monitoring data can be used to keep track of the quality of working conditions by comparing the observed risk profiles with the proposed ARL. Our study has shown that automated preparation may have an upper hand in terms of safety but still leaves room for improvement, at least in our four hospitals.

An Automated Micro Solid-Phase Extraction (µSPE) Liquid Chromatography-Mass Spectrometry Method for Cyclophosphamide and Iphosphamide: Biological Monitoring in Antineoplastic Drug (AD) Occupational Exposure.

Despite the considerable steps taken in the last decade in the context of antineoplastic drug (AD) handling procedures, their mutagenic effect still poses a threat to healthcare personnel actively involved in compounding and administration units. Biological monitoring procedures usually require large volumes of sample and extraction solvents, or do not provide adequate sensitivity. It is here proposed a fast and automated method to evaluate the urinary levels of cyclophosphamide and iphosphamide, composed of a miniaturized solid phase extraction (µSPE) followed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The extraction procedure, developed through design of experiments (DoE) on the ePrep One Workstation, required a total time of 9.5 min per sample, with recoveries of 77-79% and a solvent consumption lower than 1.5 mL per 1 mL of urine sample. Thanks to the UHPLC-MS/MS method, the limits of quantification (LOQ) obtained were lower than 10 pg/mL. The analytical procedure was successfully applied to 23 urine samples from compounding wards of four Italian hospitals, which resulted in contaminations between 27 and 182 pg/mL.

Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part I - medical gloves.

Antineoplastic drugs (ADs) are essential tools in cancer treatment, but their cytotoxicity poses a risk to workers involved in their handling. In a hospital environment fundamental strategies for minimising exposure involve proper use of safety cabinets and closed-circuit transfer devices, along with personnel training and increased awareness of risks. However, medical gloves remain the first line of defence. In this respect the evaluation of glove materials and best choices can improve hospital safety management and prevent potential hazards and long-term consequences. The aim of this study was to assess contamination of gloves in samples taken from AD administration and preparation units of nine Italian hospitals and to raise awareness of the importance of evaluating chemico-physical properties of gloves. Our findings show that 33 % of the analysed gloves were positive for at least one AD, with contaminations ranging from 0.6 to 20,729 pg/ cm2. We proposed the alert glove values (AGVs) for each AD as a limit value for contamination assessment and good practice evaluation. Our findings also point to multiple AD contamination (43 % of positive findings in preparation units), calculated as total AGV (AGV-T), and confirm that gloves should be replaced after 30 min of AD handling, based on cumulative permeation and area under the curve (AUC), to maintain safety and limit dermal exposure.

A New Perspective on SPME and SPME Arrow: Formaldehyde Determination by On-Sample Derivatization Coupled with Multiple and Cooling-Assisted Extractions.

Formaldehyde (FA) is a toxic compound and a human carcinogen. Regulating FA-releasing substances in commercial goods is a growing and interesting topic: worldwide production sectors, like food industries, textiles, wood manufacture, and cosmetics, are involved. Thus, there is a need for sensitive, economical, and specific FA monitoring tools. Solid-phase microextraction (SPME), with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBHA) on-sample derivatization and gas chromatography, is proposed for FA monitoring of real-life samples. This study reports the use of polydimethylsiloxane (PDMS) as a sorbent phase combined with innovative commercial methods, such as multiple SPME (MSPME) and cooling-assisted SPME, for FA determination. Critical steps, such as extraction and sampling, were evaluated in method development. The derivatization was performed at 60 °C for 30 min, followed by 15 min sampling at 10 °C, in three cycles (SPME Arrow) or six cycles (SPME). The sensitivity was satisfactory for the method's purposes (LOD-LOQ at 11-36 ng L-1, and 8-26 ng L-1, for SPME and SPME Arrow, respectively). The method's linearity ranges from the lower LOQ at trace level (ng L-1) to the upper LOQ at 40 mg L-1. The precision range was 5.7-10.2% and 4.8-9.6% and the accuracy was 97.4% and 96.3% for SPME and SPME Arrow, respectively. The cooling MSPME set-up applied to real commercial goods provided results of quality comparable to previously published data.

Simultaneous Determination by Selective Esterification of Trimellitic, Phthalic, and Maleic Anhydrides in the Presence of Respective Acids.

Trimellitic, phthalic, and maleic anhydrides are important building blocks to produce polymers and additives, such as plasticizers. In humans, the exposure to these compounds can cause several health issues. In European Union and USA, their presence in substances and mixtures is restricted by CLP Regulation (no. 1272/2008) and HCS/HazCom 2012, respectively, but no information about the corresponding acids is reported. For this reason, a selective method to determine anhydrides in mixtures, in the presence of acids, could be interesting. Nowadays, methods in the literature are either not selective or use explosive and toxic reagents (as diazomethane). In this work, an innovative, greener, and safer method for the simultaneous recognition and quantification of anhydrides and acids, via direct injection gas chromatography-mass spectrometry, is developed. The sample pretreatment consists in selective esterification with absolute ethanol on the anhydride, followed by a treatment with boron trifluoride-methanol for the methylation of remaining carboxylic groups. The optimization of the functionalization, a crucial step of the method, was optimized by experimental design. The limit of detection-limit of quantification (LOD-LOQ) values for trimellitic, phthalic, and maleic anhydrides are 0.31-0.93, 0.47-1.41, and 0.06-0.18 µg/mL, respectively.

Monitoring surface contamination for thirty antineoplastic drugs: a new proposal for surface exposure levels (SELs).

BACKGROUND: Chemotherapy drugs are widely used to treat cancer, but their active compounds represent a danger for workers who could be exposed to them. However, they aren't yet included in directive CE No. 1272/2008 and the European Biosafety Network has only recommended a limit value of 100 pg/cm2 for surface contamination. Thus, it is crucial to assess surface contaminations in healthcare environments. Currently, the technique of choice is surface wipe test combined with liquid chromatography tandem mass spectrometry to achieve high sensibility. MATERIAL AND METHODS: A campaign involving Careggi University Hospital (Florence, Italy) was performed from January 2020 to December 2021, collecting 1449 wipe samples between administration units, preparation unit, and personnel gloves. From the obtained data, the 90th percentile was calculated for 30 antiblastic drugs and proposed as surface exposure levels (SELs); while from data concerning personnel glove contamination, weekly contamination was estimated. RESULTS: In the 2-year period only 417 wipe samples were found positive (28.8%), the majority of which regard samples coming from administration unit bathrooms. The proposed SELs are almost all <100 pg/cm2, except for few drugs which produce higher contamination on bathroom surfaces. Also, the estimation of pharmacy personnel's glove contamination highlighted very low results (ng/week). CONCLUSIONS: Deeply established protocols and procedures for safe handling of ADs allow for obtaining excellent cleaning results and thus a safer work environment, however, the risk of cytostatic contaminations cannot be avoided in healthcare workplaces, and thus a harmonization of classification and labeling of chemotherapy drugs throughout the European Union should be done. Med Pr. 2022;73(5):383-96.

Advanced Solid-Phase Microextraction Techniques and Related Automation: A Review of Commercially Available Technologies.

The solid-phase microextraction (SPME), invented by Pawliszyn in 1989, today has a renewed and growing use and interest in the scientific community with fourteen techniques currently available on the market. The miniaturization of traditional sample preparation devices fulfills the new request of an environmental friendly analytical chemistry. The recent upswing of these solid-phase microextraction technologies has brought new availability and range of robotic automation. The microextraction solutions propose today on the market can cover a wide variety of analytical fields and applications. This review reports on the state-of-the-art innovative solid-phase microextraction techniques, especially those used for chromatographic separation and mass-spectrometric detection, given the recent improvements in availability and range of automation techniques. The progressively implemented solid-phase microextraction techniques and related automated commercially available devices are classified and described to offer a valuable tool to summarize their potential combinations to face all the laboratories requirements in terms of analytical applications, robustness, sensitivity, and throughput.