from repeated injections.
● Linearity: determined by calculation of a least squares regression coefficient for solutions applied to the LC/MS over a defined range.
● Drug recovery from the swab material: determined in triplicate by application of a known quantity of target drug applied to a wipe, the wipe then extracted and extracts tested according to the test protocol.
● Drug recovery from an impervious surface (glass plate): determined in triplicate by application of a quantity of the target drug onto the surface of a glass tile. The solvent was allowed to evaporate to dryness in a current of air. The glass tile was then wiped and the wipe processed according to the test method.
● Stability of extracts: stability of drugs following their uptake onto the swab was determined by spiking a series of wipes with the target drug and extracting at differing times up to seven days after being stored refrigerated.
● Limits of detection (LOD) and limits of quantification (LOQ): established using the signal to noise ratio (x 3 for LOD and x 10 for LOQ).
Since commencing the testing 30 aseptic units in the North West of England have performed a residues survey at least once in the course of about one year. The data
Table 3: Samples that exceed the provisional ALARA level
Level (pg/cm2 9100 5700 2860 2730 2300 2170 2010 1470 1290 1074 1000 959
Isolator work surface Clean room floor Clean room floor Clean room floor
Clean room preparation bench Clean room floor
Base of gauntlet, inside isolator Isolator hatch
Clean room floor Isolator rear wall
Isolator work surface Baffle – rear of isolator
Note: The highest cyclophosphamide residues recorded originate from only 5 out of 30 aseptic units.
residue levels from resubmitted samples. Aseptic units finding high levels of cytotoxic residues are also advised to re-evaluate their routine clean down procedures and aseptic practices. Environmental control and therefore occupational health and safety is likely to be best serviced by controlling the high-risk drugs in terms of their usage and their physical/chemical properties. In the North West of England the highest risk drug has been identified as cyclophosphamide.
Laboratory experience suggests cyclophosphamide is one of the more difficult drugs to remove by non- destructive cleaning. It has also been reported9
to be susceptible to
sublimation, presenting even greater challenges in its environmental control.
sampling. The next phase is to introduce greater standardisation of sample locations with the units directed to monitor in specific areas. This will extend to include surfaces of incoming drug containers and areas where pharmacist- releasing activities take place. With cyclophosphamide being our most extensively handled drug, it is the most useful monitor of cleanliness and environmental control. Through simple statistical analysis, the declaration of a provisional ALARA (as low as is reasonably achievable)7
level for North
West units. The level has been set at 700 pg/cm2
. Twelve out of 120 individual
“The ALARA is used to trigger a telephone call to the lead pharmacist to discuss the data and initiate a specific clean down”
from three of the most abundantly found drug residues are presented in Tables 1–3. In most cases, residues were found to be below the LOD of the analytical method. Occasionally samples have been tested showing residues several hundred times higher than the LOQ. So far there is no correlation between the incidence of high residue level to sampling position in the isolator or the room.
The laboratory has started to gather considerable amounts of data from its client base. In this survey, aseptic units were given the opportunity to decide the numbers and locations of their samples and were only trained in the technique for
samples in the survey exceeded this level (Table 3).
The ALARA is used to trigger a phone call to the lead pharmacist to discuss the data and to initiate a specific clean down. Extensive research8
has been performed
on the merits of detergent and chemical clean-down of cytotoxic residues. However QCNW has issued the following advise on cleaning when a high residue is reported: ● Clean areas thoroughly using a sterile detergent solution.
● Rinse with sterile distilled water. ● Clean using sterile 70% IPA/IMS ● Re-sample and submit to QCNW. Application of this simple process has resulted in considerable reductions in
Our cytotoxic monitoring service provides analysis of a wide range of drugs and new methods are being developed. The sensitivity of LC/MS provides the unique opportunity to monitor these compounds at ever decreasing levels thus keeping pace with improving ALARA levels. ●
References 1. Valanis B et al. Occupational exposure to antineoplastic agents: self reported miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med 1999;41:632– 638.
2. Blaha L et al. Safe handling of cytotoxic drugs: the need for monitoring and critical risk assessment. Hosp Pharm Eur 2008;40;60–63.
3. Tompa A. Hospital workplaces: risks of exposure to carcinogens. Hosp Pharm Eur 2008:36;29–31.
4. Allwood M et al eds. Cytotoxics Handbook, 4th edition. Oxford: Radcliffe Medical Press, 2002.
5. National Institute for Occupational Health and Safety. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. www.cdc.gov/niosh/
docs/2010-167/pdfs/2010-167.pdf (accessed 21 December 2011).
6. Schulz H et al. Antineoplastic agent workplace contamination study: the Alberta Cancer Board Pharmacy perspective. J Oncol Pharm Practice 2005:11:101–109.
7. Zeedijk M, Greijdanus B. Monitoring exposure of cytostatics on the hospital ward. EJHP-Science 2005;11;18–22.
8. Roberts S et al. Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Practice;2006;12;95–104.
9. Clark C. Occupational exposure to cytotoxic drugs. Pharm J 1999;263;65–67.
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