Contact Us

Contamination on Inner Walls of Syringes Used for Compounding and Administration of Hazardous Drugs

Ilya Viten on April 27, 2025

Abstract Introduction:

To evaluate contamination on inner walls of barrel syringes used for preparation and administration of hazardous drugs by means of wipe sampling.

Purpose

The aim of the study was to measure contamination on inner walls of syringes used for compounding hazardous drugs. As the syringes have an open connection to the environment, evaporation of the drugs could result in environmental contamination and potential exposure of healthcare workers.

Methods

Forty-three 50 mL BD Plastipak luer lock syringes were collected after single use in compounding hazardous drugs. The inner wall of the barrel was wiped for each syringe. Potential remaining contamination was also measured by liquid extraction to verify the effectiveness of the wiping procedure. Six hazardous drugs were tested. Liquid chromatog-raphy tandem mass spectrometry was used for the analysis of cyclophosphamide, doxorubicin, 5-fluorouracil, ifosfamide, and methotrexate. Platinum analysis of cisplatin was performed with voltammetry.

Results

Contamination was found for all cyclophosphamide, doxorubicin, ifosfamide, and methotrexate syringes, for eight out of ten 5-fluorouracil syringes, and for none of the cisplatin syringes. Contamination as part of the dose transferred differs between the drugs showing the highest contamination for doxorubicin (median 21.90 ppm) followed by cyclophosphamide (median 1.24 ppm), and ifosfamide (median 0.60 ppm). The lowest contamination was measured for 5-fluorouracil (median 0.02 ppm) and methotrexate (median 0.006 ppm).

Conclusion

Contamination was found on almost all syringes and differs between the drugs indicating some drugs stick more to the inner walls and plunger shafts than others. Contamination implies a potential exposure risk as hazardous drugs could evaporate from the open syringes, contaminate the working environment, and expose healthcare workers.

Introduction

When a syringe is filled with a hazardous drug (HD) during the compounding process, the inner wall of the syringe barrel is in contact with the drug that may react and stick to the surface. After transferring the HD to an infusion bag or pump reservoir, or after administration as a bolus injection, an open connection is created between the inner wall of the syringe barrel and the environment. Consequently, HDs may evaporate and potentially contaminate the working environment. Furthermore, the syringe plunger may get contaminated by contact with the inner wall of the syringe. The drug may also be transferred to the plunger during manipulation of the syringe. This may even increase if the syringe is used for multiple manipulations as observed in daily practices for instance if the volume for compounding exceeds the maximum volume of the syringe. Even during batch and dose-banding production, it is common to reuse syringes several times. The contamination on the plunger could finally be transferred via gloves of the pharmacy staff, nurse and other healthcare workers to other surfaces resulting in spread of contamination into the working environment and potential exposure of the workers. Obviously, this should be prevented as much as possible.


Even after compounding and administration, when the syringes are disposed, the evaporation process will continue resulting in contamination in and around the HD waste bin. If the syringes are not properly disposed (thoroughly wrapped or sealed), staff involved in transport and waste handling could be exposed.

Contamination on syringes used during drug compounding has been investigated previously but studies were mainly focused on contamination on the plungers. In 2005, Favier et al. detected cyclophosphamide on the plungers of all Becton Dickinson® syringes tested.1 In 2010, Kiffmeyer, repeated the study for Becton Dickinson®, Terumo®, and Equashield® syringes.2 Two, four or eight manipulations were performed for each syringe. The highest cyclophosphamide contamination was found on the plungers of the Becton Dickinson® syringes. In a separate test, cyclophosphamide was also detected on the inner walls of almost all Becton Dickinson® and Terumo® syringes. In 2014, Smith et al. performed a comparable study and compared syringe plunger contamination between Becton Dickinson® and Equashield® syringes.3 Two, four or eight manipulations were performed for each syringe.

A significant higher cyclophosphamide contamination was found for the Becton Dickinson® syringes compared to the Equashield® syringes. However, execution and outcome of the study were questioned and debated as the study would not reflect routine compounding conditions (multiple manipulations), statistical analysis was flawed, controls were lacking, and sample sizes were different.4–6 Recently, Barta et al. quantified HD contamination on the inner walls of standard open barrel syringes connected to the Becton, Dickinson and Company PhaSeal® Closed System drug Transfer Device (CSTD). Single manipulations were performed for fifteen syringes 5-fluorouracil, cyclophosphamide, and ifosfamide. The inner walls of all forty-five syringes were contaminated after transfer of the drug from vial to syringe to IV bag.7 In conclusion, all studies show HD contamination on plungers and inner walls of open barrel syringes after compounding indicating a potential risk for environmental contamination and exposure of healthcare workers.


The aim of our study was to evaluate contamination on inner walls of syringes used for single use compounding of HDs by means of wipe sampling and to test for more HDs. Syringes for single use compounding or manipulation are considered as daily practice. Cyclophosphamide, ifosfamide, 5-fluorouracil, doxorubicin, methotrexate, and cis-platin syringes were selected representing HDs with different physical and chemical properties such as concentration, volatility, viscosity, and affinity to syringe surfaces.


Materials and methods


The study was performed by Exposure Control Sweden AB (Bohus-Björkö, Sweden).
HD syringes tested
Forty-three 50 mL BD Plastipak luer lock syringes were collected at the pharmacy department of the University Hospitals Leuven in Belgium (Table 1). The syringes are open barrel syringes frequently used for HD compounding. The syringes were collected after single use preparation of HDs. The drugs were transferred from the vials via the syringes to the infusion bags using the ChemoClave and Spiros CSTD (ICU Medical, San Clemente, USA). Drug volumes transferred varied from 36 to 60 mL. Fourteen operators (pharmacists and pharmacy technicians) were involved in the preparation of the syringes.

Touching the plunger shafts was not allowed to avoid contamination on the inner walls of the syringes caused by the gloves of the operators during compounding. Only the external knob on the end of the plunger was used for holding. To ascertain that the plunger shaft was not touched, the wipe samples were also analysed for nine other HDs in addition to the drug handled and transferred, except for cisplatin as the sample clean up procedure and the analysis was different compared to the other five HDs tested. In this way, potential transfer of contamination by the gloves of the operators to the prepared syringes could be established.


Six HDs were tested because physical and chemical properties of drugs differ, and this could produce different results. Only 50 mL syringes were collected for testing to allow convenient access with the wipes. Considering the 50 mL requirement, the following HDs fitted into the study: 5-fluorouracil (50 mg/mL), cyclophosphamide (20 mg/mL), ifosfamide (40 mg/mL), methotrexate (100 mg/mL), doxorubicin (2 mg/mL), and cisplatin (1 mg/mL). Two till ten syringes of each HD were collected depending on the availability of the syringes during the collection period.

After drug transfer, the syringes were individually packed and sealed in a plastic mini bag. The syringes were still connected to the Spiros CSTD to avoid spills with the HDs. Each syringe was provided with a unique code and details were registered (Table 1). The syringes were stored at 2–8°C until wipe sampling, sample preparation and analysis at Exposure Control Sweden AB.


Wipe sampling procedure
Cyto Wipe Kits from Exposure Control Sweden AB were used for surface wipe sampling (www.exposurecontrol. net). To perform a proper sampling, the original wipe (45 cm×24 cm) was rolled into a cylinder-shaped wipe of 12 cm in length and about 1 cm in diameter enabling easy entering the barrel (Figure 1). The plunger was set at 10 mL to have sufficient access into the syringe barrel to be able to take the wipe sample and to avoid touching of the plunger shaft. Consequently, the inner wall between 0 and 10 mL was not wiped. After the wipe was positioned in the barrel, the syringe was positioned upright, and 5 ml 0.1% formic acid solution or 5 ml 0.5 M HCL solution (for cisplatin) was dripped on the wipe. Next, the plunger was turned around to make sure the prewetted wipe contacted the total surface of the inner wall of the syringe.

The prewetted wipes were collected and extracted with 20 mL 0.1% formic acid solution. For cisplatin 20 ml 0.5 M HCL solution was used. Total extraction volume for the wipe samples was 25 mL. After extraction, a part of the extract was used for analysis.

The remaining contamination on the inner walls of the syringes was also measured after wiping to verify the effectiveness of the wiping procedure. Thereto, the syringes were placed upright with the plunger still set at 10 mL, and 50 mL 0.1% formic acid solution was poured in the space between barrel and plunger.2 For the cisplatin syringes, 50 ml 0.5 M HCL solution was used. The liquids were removed after 60–90 min and analysed separately from the wipe samples.

The wipe samples and liquids were also analysed for nine other drugs in addition to the drug handled and transferred, except for cisplatin as the sample clean up procedure and the analysis was different compared to the other five drugs tested.

Figure 1. Cylinder-shaped wipe and syringe with cylinder-shaped wipe inside the barrel

Figure 1. Cylinder-shaped wipe and syringe with cylinder-shaped wipe inside the barrel

Liquid chromatography with tandem mass
spectrometry analysis

Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used for the analysis of cyclophosphamide, doxorubicin, 5-fluorouracil, ifosfamide, methotrexate, and the other five HDs not handled and transferred but measured to check for potential (cross)contamination on the plunger shaft (cytarabine, docetaxel, etoposide, gemcitabine, and paclitaxel). Details of the analytical method and equipment used have recently been published.8 The detection limit is 0.01 ng/mL for cyclophosphamide, cytarabine, gemcitabine, ifosfamide and methotrexate, 0.2 ng/mL for docetaxel, doxorubicin and paclitaxel, and 0.5 ng/mL for etoposide and 5-fluorouracil.

Stripping voltametric analysis

Platinum analysis of cisplatin was performed with stripping voltammetry.9 0.5 mL of the extract was destructed using hydrogen peroxide, hydrochloric acid and UV-light resulting in the formation of platinum ions. Finally, the platinum ions were analysed instead of cisplatin. Samples were analysed in duplicate including destruction step. Mean values are reported. Due to background levels of platinum, the limit of quantification is set at 0.1 ng/mL. This corresponds to 0.16 ng/mL cisplatin.

Statistical analysis

All analyses were performed in R (version 4.4.1) using the R package rstatix (version 0.7.2) for statistical tests and ggplot2 (version 3.5.1) for visualisation. Wilcoxon’s non-parametric test was used for comparison of the contamination between wipe samples and liquids for each of the HDs (Table 1). Total contamination in the syringes as part of the total amount of HD transferred and presented in ppm, was also compared between the six HDs using Wilcoxon’s test. p values were adjusted for multiple com-parison using the Holm’s method. For values below the detection limit, half of the detection limit was used. p values below 0.05 were considered as significant different.

Results

Contamination measured by wipe sampling was found on the inner walls of all cyclophosphamide, doxorubicin, ifosfamide and methotrexate syringes (Table 1). 5-Fluorouracil was detected on the inner walls of four out of ten syringes. Contamination with platinum, representing cisplatin, was not detected on the four syringes tested. Comparable results were found for the remaining contamination measured in the liquids, to verify the effectiveness of the wipe sampling procedure. Contamination was again found for all cyclophosphamide, doxorubicin, ifosfamide, and methotrexate syringes, for seven out of ten 5-fluorouracil syringes, and for none of the cisplatin syringes (Table 1).


The highest total contamination (wipe samples and liquids) was measured for doxorubicin (median 1989 ng), followed by ifosfamide (median 1204 ng), and cyclophosphamide (median 956 ng). The lowest contamination was measured for 5-fluorouracil (median 45 ng) and methotrexate (median 27 ng). Cisplatin was not detected.


For cyclophosphamide, contamination was higher in the liquids than in the wipe samples (p = 0.01), while no differences were found for the other HDs. This indicates that the wipe sampling on the inner walls was not effective. Effective wipe sampling would have resulted in higher wipe sample contamination than liquid contamination.

Contamination on the syringes with the nine other HDs, apart from the HD compounded, to check for potential transfer of contamination by the gloves of the operators, was not found for the wipe samples and the liquids indicating no HD cross contamination during collection of the syringes and sampling in the laboratory.


To compare the contamination between the six HDs, the total HD dose transferred must be calculated for each of the syringes by multiplying the HD concentration with the volume transferred. Next, the contamination as part of the total amount of HD dose transferred is calculated and is expressed in parts per million (Table 1). Median values and ranges are presented and used for statistical analysis. The highest total contamination is calculated for doxorubicin (median 21.90 ppm), followed by cyclophosphamide (median 1.24 ppm), and ifosfamide (median 0.60 ppm). The lowest total contamination is calculated for 5-fluorour-acil (median 0.02 ppm) and methotrexate (median 0.006 ppm). Significant higher contamination was found for doxorubicin compared to cyclophosphamide, ifosfamide, and 5-fluorouracil (p = 0.001), and for cyclophosphamide (p = 0.0003), and ifosfamide (p = 0.002), compared to 5-fluorouracil.

Discussion

The aim of the study was to measure contamination on inner walls of syringes by means of wipe sampling. Contamination was found on all doxorubicin, methotrexate, cyclophosphamide and ifosfamide syringes. A few 5-fluorouracil syringes were also contaminated but none of the cis-platin syringes. Although the focus was to wipe the inner walls of the syringes, it cannot be excluded that the contamination measured also includes contamination on the plunger shaft.


The effectiveness of the wipe sampling procedure was validated by measuring the remaining contamination on the inner walls of the syringes after wiping. Thereto, a liquid was poured into the barrel enabling the remaining drug to dissolve. However, the results show higher amounts of drugs in the liquids than in the wipe samples, except for the cisplatin syringes where no contamination was found. This indicates that the wipe sampling procedure was less effective than the use of the liquid. In addition, contamination could also be present on the plunger shafts. As the wipes also touch the plunger shafts, contamination on the plunger shafts will be sampled too. This also concerns sampling with the liquids.


Each syringe (except for cisplatin) was also checked for contamination with nine other drugs to measure potential transfer of contamination by the gloves of the operators to the plunger shafts. No other drugs were detected except the ones compounded. This indicates that it is very unlikely that the measured contamination on the inner walls and plunger shafts of the syringes is caused by other (previous) activities than the compounding itself. It also shows that the syringes were properly collected and that the wipe testing and the collection of the liquids at the laboratory was performed without contamination.


It should be noticed that the inner walls of the syringes were not wiped between 0 and 10 mL as the plunger was set at 10 mL to perform the wipe sampling. This indicates an underestimation of the contamination with about 20 percent based on the volume transferred (median 50 mL; range 36–60 mL).


The results were not corrected for recovery, and it remains unclear if all drugs were removed by the wipes or were present in the liquid. Laboratory test performed in duplicate give some indication and show high recoveries for cyclophosphamide (96%) and ifosfamide (92%), moderate recoveries for cisplatin (80%), methotrexate (69%) and 5-fluorouracil (62%), and low recoveries for doxorubicin (19%). This indicates that some drugs stick more to the inner walls of the syringes than others especially doxorubicin. Differences can be explained by different product characteristics such as physical and chemical properties of the drugs.


The main limitation of the study concerns the ineffective wipe sampling, but this was compensated by the additional extraction of HDs on the inner walls and plunger shafts. In addition, it remains unknown whether, and how much of each HD will evaporate from the inside of the syringes and will finally be transferred as contamination into the environment.


Some (parts of the) drugs might permanently stick on the inner walls and plunger shafts of the syringes and will not be released into the environment. Despite these uncertainties, the total amount of HD contamination on the inner walls and plunger shafts of the syringes is relevant as they indicate a potential risk for environmental contamination and exposure of healthcare workers. Evaporation of HDs has been proven at room temperature in addition to release of HD particles during com-pounding.12–16


Considering the hierarchy of controls to protect workers from exposure to HDs, the focus must be on engineering controls (level 3) to isolate workers from the HDs as elimination (level 1: remove the HDs) and substitution (level 2: replace the HDs) are impossible.10,11 Patients need HDs for treatment. Administrative controls (level 4) and finally PPE (level 5) are the next steps but considered as the least effective in protection of healthcare workers. Engineering control measures, to minimise the potential spread of contamination from the inner walls and plunger shafts of the syringes to the environment, could include:

/ Single use compounding of the syringes (draw and push once).

/ Wrap or seal the syringes immediately after use. This includes transfer from vials in bags and pump reservoirs during compounding and after administration to patients.

/ Make sure the syringes are properly wrapped or sealed when discarded in a hazardous waste bin, to avoid contamination by vapours and particles from HD waste.

/ Do not use open barrel syringes but sealed syringes. Following these recommendations could result in reduction of environmental contamination and potential exposure of the operators and nurses.

Following these recommendations could result in reduction of environmental contamination and potential exposure of the operators and nurses.

Conclusion

This study has shown that routine HD compounding has resulted in contamination on the inner walls and plunger shafts of syringes for five out of six HDs tested. Some HDs stick more to the inner walls and plunger shafts than others resulting in differences in contamination between the HDs. However, most important is that the contamination on the inner walls and plunger shafts of the syringes could result in release of the drugs into the working environment and exposure of the healthcare workers. This phenomenon should be considered in taking risk management measures when handling HDs.

Acknowledgements
Statistical support from Björn Andersson and Jari Martikainen (Statisticians at the Bioinformatics and Data Centre at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden), is kindly acknowledged.


Author contributions
All authors designed the study; PS and BT, collected the data; PS, performed the analysis and interpreted the results; PS, drafted the manuscript. All authors reviewed and approved the final version of the manuscript.


Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for the research and writing this publication was provided by Equashield Medical Ltd, Migdal Tefen, Israel.


ORCID iD
Paul Sessink https://orcid.org/0000-0002-8580-0044

An Assessment of Exposed Syringe Inner Walls as a Route of Exposure from Hazardous Drugs

Ilya Viten on March 19, 2025

Abstract Introduction:

Maintaining safe working environments for health care personnel, especially for those who regularly handle hazardous drugs (HDs), is of utmost importance. Studies have shown that when closed system transfer devices. (CSTDs) are used with standard open barrel syringes, cyclophosphamide (CP), a commonly used HD, is transferred to the syringe plunger during compounding or administration processes. This contamination can then be transferred to the work environment, endangering workers.

Purpose:

The purpose of this study was to quantify HD contamination of the inner surface of standard open barrel syringes and to compare contamination levels between three commonly used HDs: 5-fluorouracil (5-FU), CP, and ifosfamide (IF).

Methods:

Each HD was transferred from a vial to an intravenous (IV) bag using a standard open barrel syringe and Becton, Dickinson and Company (BD) PhaSealTM CSTD connectors. Samples were taken from the inner surface of each of the syringe barrels to measure the amount of HD contamination. Each drug was tested 15 times and compared to a positive control.

Results:

Significant amounts of each drug were transferred to the inner surfaces of the syringes. The average amounts of each drug measured were: 5-FU, 1327.7 ng (standard deviation [SD] =873.6 ng); CP, 1074.8 ng (SD=481.6 ng); and IF, 1700.0 ng (SD =1098.1 ng). There was no statistically significant difference between the three drugs (p=0.14).

Conclusion:

This study underscores the presence of HD contamination on standard open barrel syringe inner surfaces after transfer of drug from vial to syringe to IV bag. Such contamination could be spread in the working environment and expose health care workers to harm.

1. Introduction

Hazardous drugs (HDs), as defined by the National Institute for Occupational Safety and Health (NIOSH), are Food and Drug Administration approved medications that meet certain toxicity criteria for humans or animals. These drugs have been determined to be carcinogenic, reproductively toxic, developmentally toxic, genotoxic, and/or toxic to specific organs (e.g., heart, lungs, kidneys, liver).1,2 Common HDs include antineoplastic agents (e.g., 5-fluorouracil [5-FU], cyclophosphamide [CP], and ifosfamide [IF]), nucleosides and nucleotides (e.g., ribavirin), immunosuppressive agents (e.g., tacrolimus), disease-modifying antirheumatic agents (e.g., leflunomide), hormone-based therapies (e.g., estradiol), and other non-neoplastic agents.3

HDs pose risks not only to patients receiving them therapeutically but also to the health care personnel who compound, administer, transport, dispose, and/or otherwise handle them.1,2 Exposure to such drugs can occur through skin and mucosal membrane absorption, inhalation, incidental ingestion, or via needle stick. HD exposure may, in turn, cause adverse effects including skin rashes, infertility, and cancer.2,4–6

Thus, preventing exposure of health care workers to HDs is of utmost importance for maintaining a safe working environment. This can be achieved through the use of engineering controls, personal protective equipment (PPE), and administrative controls.2 Closed system transfer devices (CSTDs) are one type of engineering control. These needleless devices allow HD manipulations to occur within a closed system, thus protecting health care workers from undue exposure.

If a CSTD is designed well, manufactured properly, and used appropriately, it should protect health care workers from HD exposure during the compounding and administration of HD products. All CSTD syringe adapters require the use of a syringe, which depending on its design, may compromise the closed nature of a CSTD system. The open barrel of a standard syringe can potentially lead to environmental contamination, and thus danger to health care workers. The extent of contamination possible is dependent on the drug used and its volatility, concentration, viscosity, and affinity for the syringe surface.7,8

Unlike standard open barrel syringes, sealed barrel CSTD syringe units are designed to provide a completely closed system. The typical use of any HD requires filling a syringe with the drug and transferring it to an intravenous (IV) bag or IV administration line. During the process of drawing a HD from a vial into a syringe, the HD comes into direct contact with the inner wall of the syringe for a period of time. Through this exposure, the HD may adhere to the syringe surface by chemical affinity or cohesive–adhesive forces. After the drug is transferred from the syringe, the inner surface—and any residual HD adhering to the inner surface—becomes exposed to the environment.

Potential contamination of the working environment with the HD may occur by two possible routes: evaporation of the HD or direct contact with the inner wall of the syringe. The latter type of contamination could then be spread to the working environment or health care worker via gloves or direct contact with other surfaces. This method of contamination should be prevented as much as possible and ideally, should not occur during the handling of any HD. Different levels of contamination may be observed with different HDs due to the unique physical and chemical properties of each drug; however, any level of HD contamination is a reason for concern.

Studies using CSTDs in the compounding and administration of HDs have shown a significant reduction in surface contamination levels.9,10 However, detectable levels of HDs have been observed with the use of some CSTDs. This suggests that some systems are not entirely closed or if the system is closed, there are other ways people can become exposed. Ultimately, health care workers remain at risk of exposure with their use.10,11 One study using a surface monitoring technique explored environmental contamination via syringe plunger contamination during routine drug preparation in hospital pharmacies.7

Contamination by CP on a standard open barrel syringe plunger was confirmed, localized, and quantified. Result from additional studies have confirmed the transfer of CP to a standard syringe plunger.8,9 In these studies, drug residuals on the syringe plunger contaminated both gloves and the work environment.

The purpose of this study was to quantify HD contamination of the inner surface of standard open barrel syringes and to compare contamination levels between three commonly used HDs: 5-FU, CP, and IF.

2. Methods

Three common HD products were prepared under real world compounding conditions to measure contamination levels of the inner walls of standard open barrel syringes. Using a modified NIOSH performance protocol for CSTDs,12 a total of 50 mL of drug was transferred from a vial to a 50 mL open barrel syringe, and then from the syringe to an IV bag, using the appropriate vial, syringe, and IV bag CSTD connectors. The drugs evaluated were 5-FU (50 mg/mL), CP (20 mg/mL), and IF (50 mg/mL). Becton, Dickinson and Company (BD) PhaSealTM CSTDs were used for each of the drug transfer manipulations.

The research team was comprised of a pharmacy school faculty member with extensive cleanroom experience, a pharmacy student with aseptic technique training, and a senior research associate with a doctorate in pharmacy. United States Pharmacopeia General Chapter <800> standards for protecting health care workers from HDs were adhered to throughout the testing (e.g., use of PPE, ventilated hoods, and biosafety cabinets).13

ChemoGLOTM HDClean Wipes were used for sampling the inner surfaces of the syringes, and all data were recorded on the ChemoGLOTM Site Map Form.14 Once completed, the ChemoGLOTM Site Map Forms, along with the correspondin wipe samples, were submitted to the ChemoGLOTM laboratory for analysis (Chapel Hill, North Carolina).

For each test, a CSTD vial adapter was attached to a vial containing the HD being tested, a CSTD bag adapter was attached to an IV bag, and a CSTD syringe adapter was connected to a standard open barrel syringe. The drug was then reconstituted according to the manufacturer’s instructions, if needed (i.e., CP and IF). The syringe was then attached to the vial via the CSTD adapters, and 50 mL of drug was drawn into the syringe. The 50 mL of drug was then injected into the IV bag via the CSTD IV bag adapter. Once each IV bag was prepared, the syringe barrel was tested for the presence of HD contamination.

To test the inner surface of each syringe used, a ChemoGLOTM wipe was used to wipe all four quadrants of the syringe barrel according to the following process:

  • A quarter from the plunger barrel knob was removed,
    allowing for controlled and easy access to the syringe
    barrel without interference from the syringe plunger.
    This allowed for wiping the exposed inner wall of the
    syringe.
  • A wipe was placed into the open section, and a wooden
    rod was used to move the wipe up and down.
  • The syringe plunger rod was rotated 90 degrees, and the
    process was repeated to ensure that the entire syringe
    barrel was wiped.
  • An additional ChemoGLOTM wipe was used to swab
    each syringe quadrant a second time, using the same
    method.
  • Each wipe was then packed and labeled according to the
    instructions provided in the sampling kit.

Each test was repeated 15 times for each of the three drugs, for a total of 45 tests. The sample size of 15 syringes was based on sample sizes used in similar studies.7,8 The use of a full 50 mL per injection was also based on previous studies.7,8


Positive controls for each drug were also tested by inoculating a syringe barrel with the drug, followed by wipe sampling the inner wall of the syringe using the same method described above. No negative controls were tested since the ChemoGLOTM wipe sampling procedure is a validated process that does not require a negative sample.15

The lower limit of quantitation of the ChemoGLOTM assay is 10.0 ng/ft2 (0.011 ng/cm2) per drug, and the upper limit of quantitation (ULQ) is 4000.0 ng/ft2 (4.31 ng/cm2).16 The total drug amount found on each syringe tested was determined by adding the amounts from the two wipes used for sampling (wipe 1 plus wipe 2).

Since there were three independent groups of data and the 5-FU and IF data were not normally distributed, a Kruskal–Wallis test using a 0.05 significance level was applied to the ChemoGLOTM test results to determine if there was a statistically significant difference in contamination levels between the three HDs tested. Statistical and, descriptive analyses were performed using GraphPad Prism 10.0.2 (232) software.

Results

The results of this study found the inner surfaces of all 45 syringes contaminated with the HD being tested. The average amount of 5-FU detected by the ChemoGLOTM wipe kit for the 15 syringes tested was 1327.7 ng (standard deviation [SD]=873.6 ng). The average amount of CP detected was 1074.8 ng (SD =481.6 ng), and the average concentration of IF detected was 1700.0 ng (SD=1098.1 ng). The positive controls for each drug resulted in measurements exceeding 4000.0 ng each, indicating amounts beyond the test’s ULQ. Based on previous work by Cox et al., the percent recovery of the drug on each surface is estimated to be >95%.15 See Table 1 for a complete list of the data collected.


The Kruskal–Wallis test performed on the data revealed that there was no statistically significant difference between the different drugs’ level of contamination (p=0.14).

Discussion

The results from this study found significant contamination by each of the three drugs on the inner walls of the open barrel syringes. The difference in level of contamination between the three drugs was not statistically significant, highlighting that inner surface contamination by most HDs is likely when open barrel syringes are used during compounding and administration. Any differences that would exist between different HDs would likely be due to the different chemical and physical properties of the drugs —such as their polarity, hydrogen bond donor and acceptor count, and viscosity—and their relative affinity for the syringe surface. A higher SD, as is the case of IF, indicates greater variability in contamination levels.

These findings align with results from other studies. One study that assessed the extent of CP contamination on syringe plungers showed contamination in amounts ranging from 3.7 to 445.7 ng when tested via gas chromatography/ mass spectrometry (GC/MS).7 Another study, using ChemoGLOTM wipe test sampling, found CP contamination levels greater than 2000 ng on open barrel syringe plungers and no detectable contamination on sealed barrel syringe plungers after a 50 mL aliquot of CP was drawn into each syringe and injected back into the CP vial multiple times.8 The difference in this study’s CP results from these two studies’ results is likely due to the differences in analytical tools used (GC/MS vs. ChemoGLOTM wipe tests), the number of times CP was drawn into each syringe (multiple times vs. once), and/or the sampling techniques used.

One of the limitations of this study was that the positive controls for each drug resulted in measurements of greater than 4000 ng each. Since the ChemoGloTM assay has an ULQ of 4000.0 ng, the true amount of drug could not be determined for the controls. The amount of residual drug could have been anywhere from 4000 ng to orders of magnitude more. Therefore, even though the contamination of the syringe barrels from these three drugs can be quantified and compared via this testing method, the full clinical significance of the results cannot be determined by this
study alone.

Additionally, a full 50 mL of drug was drawn into each 50 mL syringe to maximize exposure of the syringe’s inner surface to the drug. This type of usage is not standard compounding practice and may have caused an overestimation of the amount of residual drug that would typically be left on the syringe inner wall during sterile product preparation or administration. Therefore, these results may not be fully generalizable to common compounding practices.

The difference in concentration of the CP solution versus the 5-FU and IF preparations could also have affected the relative amount of drug adhering to the syringe wall. However, the drug preparations used in this study (50 mg/mL for 5-FU, 20 mg/mL for CP, and 50 mg/mL for IF) are standard compounding concentrations, so these results reflect real-world comparisons, enhancing their generalizability.

Finally, only three HDs drugs were tested in this study, allowing for the possibility that additional HDs with different chemical and physical properties could produce different results.

Additional studies are warranted to analyze the extent of contamination after multiple transfers and with extended duration of use, both of which may increase the potential for HD exposure. Understanding the extent of contamination with such use would better reflect the risks associated with real-world compounding practices. Also, further studies examining the extent of transfer of HD from a syringe inner wall to a user’s gloves and compounding working space for these three drugs and other HDs are needed to better understand the extent of risk to health care workers with the use of open barrel syringes.

Conclusion

This study underscores the presence of HD contamination on standard open barrel syringe inner surfaces after transfer of drug from vial to syringe to IV bag. The detected amounts of each the three drugs (5-FU, CP, and IF) on the inner surface of standard open barrel syringes were high (ranging from 1074.8 to 1700.0 ng), especially given that the maximum amount measured (for one sample of IF) exceeded the ULQ set by the ChemoGLO assay at 4000.0 ng. Such levels of drug contamination are of concern since they could be transferred to the working environment and expose health care workers to harm. Identifying ways to limit contamination and exposure is important for the safety of all health care workers who regularly handle HDs.

Authors’ contribution

BTB and SFE conceived the study and were involved in protocol development and data collection. All authors researched literature and performed data analysis. LTA wrote the first draft of the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

Declaration of conflicting interests

Equashield® provided the funding and proposed the general framework of the study. SFE and LTA have also received funding support from BD, Daiwa Can Company, and Shandong Ande Healthcare Apparatus Co., Ltd. for additional CSTD-related research. SFE is a co-founder of ChemoGLOTM. The authors declare no additional conflicts of interest.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Equashield®.


ORCID iD

Lori T Armistead https://orcid.org/0000-0002-4680-0156

Products

How CSTD Works?

Solutions

EQ Academy

Company

Ordering Information

Contact Us