HSE Science and Research Centre are able to offer an analysis
service for biological monitoring and surface wipe sampling for
cytotoxic drugs. We have also publsihed a number of papers on
the topic. (all are freely available from the links provided). HSE
also provides guidance on the
safe handling of cytotoxic drugs in the workplace.
Mason HJ, Blair S, Sams C, Jones K, Garfitt SJ, Cuschieri MJ,
Baxter PJ. Exposure
to antineoplastic drugs in two UK hospital pharmacy units. Ann
Occup Hyg. 2005 Oct;49(7):603-10.
Mason HJ, Morton J, Garfitt SJ, Iqbal S, Jones K. Cytotoxic
drug contamination on the outside of vials delivered to a hospital
pharmacy. Ann Occup Hyg. 2003 Nov;47(8):681-5.
Ziegler E, Mason HJ, Baxter PJ.
Occupational exposure to cytotoxic drugs in two UK oncology
wards. Occup Environ Med. 2002 Sep;59(9):608-12.
In addition to hospital pharmacies and exposures in healthcare,
there is increasing use of cytotoxic drugs in the veterinary
sector. Some
general guidelines were presented at the British
Small Animal Veterinary Congress in 2008. Surface wipe
testing and biological monitoring may also have roles to play here
in assessing the adequacy of control.
Surface wipe testing
Surface wipe testing is a practical means of testing the level
of contamination external to enclosures, such as isolators or
safety cabinets. Any such contamination is a possible source
of exposure to staff. A monitoring strategy based on surface
wipe testing can help benchmark the combined effectiveness of
containment work practices, operating and cleaning procedures in
reducing the risk to staff. Any monitoring may be carried out
annually or six-monthly using an identical procedure. It can also
be used to identify the effect of any implemented changes.
This note details a procedure for determining cytotoxic drug
contamination on surfaces. It is based on monitoring of one
or more "marker" drugs that may be used as surrogates of the
general level of contamination. Recently we have
reduced the number of high sensitivity analytical methods for
cytotoxic drugs due to limited demand. We now offer
platinum for the platino-coordinated drugs such as
cis-platin and carboplatin (Pt), cyclophosphamide
(CP) and ifosfamide (Ifos).
Analysis of the drugs uses high sensitivity ICP-MS or LC-MS
techniques, and the methods were specifically developed for low
levels that may be found outside laminar flow cabinets,
microbiological safety cabinets or isolators, rather than the level
of contamination that may be found inside such enclosures.
Methods for these specific marker drugs have been developed as they
are widely used in anti-neoplastics/cytotoxic
pharmaceuticals. The choice of one or more marker drugs to be
monitored will depend on the amounts of cytotoxics being routinely
used and any specific work practices. It is not necessary to
measure all marker drugs.
We recommend wipe testing of defined, measured areas. Any repeat
testing should ideally test the same defined area. Results
are expressed as levels of contamination per wipe, which can then
be converted to contamination per sq. centimetre or sq.
metre. Details of wipe testing are shown below.
We have an increasing amount of information from various
cytotoxic sampling exercises that allow interpretation of the
results. Biological monitoring measurements based on urine samples
to quantify any absorption are also available for these marker
drugs.
Surface samples may be taken from the floor, and other surfaces
such as workbenches, desks, fittings etc. Where samples are
taken from will depend largely on the reason for the sampling, and
the size and layout of the facility. An appropriate general
sampling strategy may be to take samples from two distinct floor
areas and one work surface such as desk or bench, depending on
layout. One of the defined floor areas may be directly under
the glove ports of an isolator or the front of a safety
cabinet. Other areas such as shelving and areas of pharmacy
stores may be tested in some circumstances.
We recommend that sampling is carried out at the end of a
working day before any cleaning is carried out and that a note of
the amount of marker drug(s) formulated that day is recorded.
We can supply the necessary sampling kits (our standard kit
includes 10cm x 10cm template, solvent, wipe, screw-cap bottle,
disposable gloves to be worn while sampling and labelling for
return of samples to the laboratory). The table below details the
procedure. One area may be sampled and the wipe sample tested for
various cytotoxic drug combinations - see table below. One blank
sample per batch should also be submitted for analysis. We
will include an extra wipe kit with the kits you request - this
should be left unopened and submitted with your samples and
labelled "blank". We recommend you contact the laboratory to
discuss any aspect of a cytotoxic surface monitoring strategy.
If samples are sent to the laboratory directly after being
collected, no special storage conditions are required and samples
should be sent by first class post or courier. If storing
samples for up to five days before sending to the laboratory then
samples should be refrigerated during storage. If storing for
longer than five days, samples should be frozen prior to despatch
although it is not necessary to transport to the laboratory as
frozen or refrigerated. It is useful if details of the areas wiped
accompany the samples.
| Surface |
Method for sampling. Remember to wear disposable gloves
while carrying out wipe testing and dispose of gloves
appropriately. |
| Floor (large area) |
Measure and mark out an area 70cm x 70cm square. Pour
10ml of the appropriate wetting solvent* in the middle of the area
and wipe thoroughly with two of the wipes folded. Wipe the whole
area firmly and thoroughly until dry, a third or fourth wipe may be
needed to fully dry and clean off the area. Place all the wipes
into the screw cap bottle; label accordingly including area
wiped |
| Bench/desk/Floor small area |
Measure and mark out an area of 10cm x 10cm (or use
template). Pour 0.5 ml of the appropriate wetting
solvent* in the middle of the area or wet a folded wipe with 0.5 ml
and wipe thoroughly until the surface appears dry. A second wipe
may be needed. Place the wipes into the screw cap bottle and label
accordingly, including area wiped. |
|
Small surfaces
|
If possible measure a 4cm x 4cm area. Wet one end of cotton bud
with appropriate wetting solvent* and squeeze off any excess. Use
to wipe over the identified area. Use dry end of cotton bud to
remove any remaining solvent on the surface. Place cotton bud in
screw cap bottle and label accordingly |
* This is either 10mM bicarbonate or 50% methanol, see table
below for test combinations and appropriate wetting solvent for
wiping.
Drug measurements - compatible combinations
from a single area wipe and solvent to be used:
| Wipe solvent supplied |
Pt |
CP/Ifos |
| 10mM bicarbonate |
Yes
|
Yes
|
| 50% methanol |
No
|
Yes
|
Analytical method details:
| Parameter |
Method |
Detection Limit
(ng per wipe)
|
Precision |
| Cyclophosphamide |
LC-MS/MS
|
5
|
17%
|
| Ifosfamide |
LC-MS/MS
|
5
|
10%
|
| Platins (total) |
ICP-MS
|
0.1
|
5%
|