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.
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.
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/ cm
. We proposed the
(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.
Solid-phase microextraction (SPME) via on-fiber derivatization with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBHA) and gas chromatographic determination is considered a technique of choice in ...many analytical fields for formaldehyde (FA) monitoring. Vapor phase adsorption models of experimentally loaded PFBHA on porous divinylbenzene (DVB) SPME were investigated at 60 °C, 35 cm s-1 of air velocity, in a 1-64 min range: with the fiber completely exposed, loaded PFBHA was about 276 µg. Among the models tested, i.e. heat transfer, pseudo-second-order (PSO), Elovich, intra-particle diffusion, extra-particle diffusion and Langmuir, PFBHA adsorption was best fit by the PSO model, showing agreement with experimental data (272 µg). The sampling rate of FA in our conditions, obtained with a permeation tube system, was in agreement with literature (17.4 and 18.3 mL min-1, respectively). Thus, an overall standardization of the sampling phase is presented, leaving the sampling time as the most crucial parameter to be set for future applications.
Formaldehyde (FA) is a carbonyl compound, ubiquitous in the environment and among the most widespread pollutants: it has exhibited toxic properties and is classified as a human carcinogen. FA is ...released from several sources, both temporary (e.g., combustion processes) and permanent (e.g., building products). This work proposes an innovative fully-automated application of headspace solid-phase microextraction (SPME) with on-fiber derivatization for the analysis of airborne FA emitted from liquid solutions or solid manufacts, in static mode, via gas chromatography-mass spectrometry. The method was tested in a wide range of airborne FA concentrations, using SPME and SPME Arrow fibers: the inter-day LOD and LOQ for SPME and SPME Arrow were evaluated, resulting in 0.072 and 0.215 ppm and 0.014 and 0.042 ppm, respectively. Moreover, other conventional detectors, such as Electron Capture Detector (ECD), Thermoionic Specific Detector (TSD), Photoionization Detector (PID), and Flame Ionization Detector (FID), were tested to set an analytical method to meet different requirements. The sensitivity and linearity of PID, FID and MS were comparable, while TSD and ECD were not suitable for the developed method, due to issues of response or linearity. MS results to be the most suitable and perfoming detector, however PID and FID result to be cheaper valid alternatives.
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.
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.
To date, formaldehyde (FA) is one of the more common chemicals and its use is widespread around the world in different sectors, especially in chemical facilities and health care. FA is widely used in ...working activities owing to its chemical and physical properties. However, it also represents a concerning hazard for the workers’ health due to its toxicity and recognized carcinogenicity. The FA exposure evaluation in occupational setting has arisen interest in the scientific community that leads to the development of several analytical instruments in order to assess both long term and short-term exposure. The paper presents and discusses an equivalence tests procedure via the 2.4-dinitrophenylhydrazine (DNPH)-active air sampling formaldehyde (FA) reference method and two non-reference instruments based on continuous, direct reading monitoring, namely ProCeas® (AP2E) and NEMo XT (Ethera). The FA standard atmosphere calibration system was used to check the reference method by Pearson’s test. Subsequently, the Passing-Bablok test was carried out between the non-reference methods and the DNPH method for potential systematic or proportional errors, and finally the Bland-Altman plot was applied to determine the mean bias and the variances of the recorded values by the reference and non-reference methods in on-field sampling. The results showed a good correlation between the non-references method and the DNPH ones, suggesting their possible applications in heterogeneous occupational scenarios.
Sve do danas formaldehid (FA) često je korištena kemikalija a njegova je uporaba raširena diljem svijeta u različitim sektorima a naročito u kemijskim pogonima i zdravstvu. FA se mnogo koristi u raznim radnim postupcima radi svojih kemijskih i fizikalnih svojstava. Međutim, njegova toksičnost i karcinogeničnost predstavljaju opasnost po zdravlje radnika. Istraživanje izlaganja FA-u u radnom okružju predmet je zanimanja znanstvene zajednice i rezultira razvojem više analitičkih instrumenata kojima se utvrđuje njegov učinak na zdravlje nakon duljeg i kraćeg izlaganja. U radu je predstavljen i opisan postupak za test ekvivalencije pomoću FA referentne metode 2.4 dinitrofenilhidrazin (DNPH) -aktivnim uzimanjem uzoraka i dva nereferentna instrumenta temeljena na kontinuiranom izravnom praćenju očitanja, ProCeas® (AP2E) i NEMo XT (Ethera). Korištena je sustav za FA standardnu kalibraciju kako bi se referentna metoda provjerila pomoću Pearsonovog testa. Zatim je napravljen Passing-Bablok test između nereferentnih metoda i DNPH metode za otkrivanje mogućih sistemskih i proporcionalnih pogrešaka, a na kraju je izrađen Bland-Altman grafikon za određivanje srednjeg odstupanja i varijacija u vrijednostima dobivenima referentnim i nereferentnim metodama uzorkovanja na terenu. Rezultati su pokazali dobru korelaciju između nereferentne metode i DNPH metoda, naznačujući moguće primjene u raznorodnim radnim uvjetima.
Formaldehyde (FA) is a hazardous chemical, highly used in the anatomical pathology laboratories. The adverse health effects related to FA occupational exposure are generally related to long-term ...exposure, however the short-term exposure to peak concentrations are equally of high concern. The occupational monitoring commonly uses the 8h-Time Weight Average (TWA) metric to assess the exposure, but for those chemicals with acute effects, also the15min short-term exposure is strongly recommended. In this study, the occupational monitoring was carried out in an anatomical pathology laboratory with an in-continuous, instantaneous, and direct reading instrument for 65 work shifts (WS). In none of these, the FA European Union (EU) TWA occupational limit (620 g/m3) was exceeded. Differently, in 40 WS the EU Short Term Exposure Limit (STEL) (740 g/m3) was exceeded, even several times a WS. In sight of this, the 8h-TWA metric only could give poor information of the exposure scenario, involving peak emissions, then a 15min peak exposure assessment, via in continuous monitoring, could help managing the risk. In addition, using the inference equation, an Action Value (AV) of the 8h-TWA above which the 15min measurements are strongly recommended, equal to 23.1 g/m3, is suggested for FA.
Formaldehid (FA) je štetna kemikalija koja se vrlo često koristi u anatomskim patološkim laboratorijima. Loši utjecaji FA na zdravlje zaposlenika izloženih toj tvari općenito se povezuju s dugotrajnom izloženošću, iako je i kratkotrajna izloženost vršnim koncentracijama vrlo zabrinjavajuća. Za praćenje utjecaja obično se koristi mjerenje prosjeka 8 h vrijeme-težina (TWA) kako bi se procijenila izloženost, no za kemijske tvari koje imaju akutno djelovanje izrazito se preporučuje izračun utjecaja 15-minutne kratkotrajne izloženosti. Istraživanje praćenja utjecaja FA na radnom mjestu provedeno je u jednom patološkom laboratoriju pomoću kontinuiranog, trenutnog i izravnog očitanja mjernim intstrumentom u 65 radnih smjena (WS). Ni u jednoj EU granica TWA od 620 g/m3 nije bila viša. Nasuprot tome, u 40 radnih smjena prijeđena je EU granica kratkotrajne izloženosti (STEL) od 740 g/m3 i to više puta tijekom radnog vremena. Ako se ovo uzme u obzir, 8-satno TWA mjerenje daje samo šture podatke o scenariju izloženosti vršnim emisijama i o 15-minutnim procjenama najviše izloženosti, dok bi kontinuirano praćenje više pomoglo upravljanju rizikom. Uz to, preporuka za FA jest korištenje inferencijalne jednadžbe Akcijska vrijednost (AV) za 8 h-TWA iznad 23.1 g/m3.
