Agriculture Reference
In-Depth Information
identified (at least 3 IPs earned) authorised substance at
a concentration in excess of the MRL?' In this case, the
level of interest is the MRL. Thus, if the MRL for an
authorised substance is 100 µg/kg, CCα will be higher
than the MRL (e.g. 115 µg/kg). The numerical differ-
ence between the MRL and CCα reflects the measure-
ment uncertainty of the analytical method. If an analysis
of a sample shows that it contains an identified drug at a
concentration equal to CCα, there is a 95% certainty
that the sample contains the drug at a concentration in
excess of the MRL.
For unauthorised substances
, α is set at 0.01 and β at
0.05. In the case of unauthorised substances, the deci-
sion that needs to be taken is, 'Does this sample contain
an identified (at least 4 IPs earned) unauthorised sub-
stance?' In this case, the level of interest is zero. Thus,
for an unauthorised substance, CCα will be higher than
zero (e.g. 0.05 µg/kg). The numerical difference between
zero and CCα reflects the measurement uncertainty of
the analytical method. If an analysis of a sample shows
that it contains an identified drug at a concentration
equal to CCα, there is a 99% certainty
1
that the sample
contains the drug. If the authorised substance has an
established MRPL, CCα and CCβ should both be less
than the MRPL.
Table 13.4
Maximum permitted tolerances for relative ion
intensities using a range of mass spectrometric techniques
Relative
intensity (%
of base peak)
Electron impact -
GC-MS (relative)
Chemical ionisation -
GC-MS, GC-MS
n
, LC-MS,
LC-MS
n
(relative)
>50%
±10%
±20%
>20-50%
±15%
±25%
>10-20%
±20%
±30%
≤10%
±50%
±50%
solutions or from spiked samples, at comparable concen-
trations, measured under the same conditions, within
the tolerances specified in Table 13.4.
Performance characteristics
As stated earlier, the EU does not require the adoption
of 'official methods' for the control of residues. Member
states and their control laboratories are free to adopt
whatever methods they wish, providing that they meet
the criteria set out in Commission Decision 2002/657/
EC (2002). This document has replaced the concepts of
limit of detection and the limit of quantification with
the performance-based concepts of CCα and CCβ, as
described in ISO 11843. This can cause some confu-
sion until it is clear that these parameters relate to per-
formance of the method at the 'level of interest'. The
level of interest depends on whether the substance is
authorised
(when the level of interest is the MRL, does
this sample contain the drug at a concentration above
or below the MRL?) or
unauthorised
(when the level of
interest is zero, does this sample contain the drug?).
CCα
,
the decision limit
, is defined as the concentration
at and above which it can be concluded with an error
probability of α that a sample is non-compliant. For
most purposes, CCα is the more important parameter as
it is the point at which a sample is deemed to be
non-compliant.
CCβ
,
the detection capability
, is the smallest content of
the substance that may be detected, identified and/or
quantified in a sample with an error probability of β. In
the case of substances for which no permitted limit has
been established, the detection capability is the lowest
concentration at which a method is able to detect truly
contaminated samples with a statistical certainty of 1 − β.
In the case of substances with an established permitted
limit, this means that the detection capability is the con-
centration at which the method is able to detect permitted
limit concentrations with a statistical certainty of 1 − β.
For authorised substances
, α and β are both set at 0.05.
In the case of authorised substances, the decision that
needs to be taken is, 'Does this sample contain an
Method validation
Commission Decision 2002/657/EC (2002) requires that
analytical methods be validated and provides guidelines
for validation. In common with other validation proto-
cols, recovery, repeatability and within-laboratory repro-
ducibility need to be determined. The document outlines
procedures that may be adopted to measure these
parameters.
For authorised substances, a set of samples of speci-
fied test material (identical or different matrices), forti-
fied with the analyte(s) 0.5, 1.0 and 1.5 times the MRL, is
prepared. For compounds with an established MRPL, at
least three levels around the MRPL (e.g. 0.5, 1.0 and 1.5
times the MRPL) should be chosen. Where MRPLs have
not been set for a particular unauthorised substance, the
levels chosen should be as low as reasonably achievable.
At each level, the analysis should be performed with at
least six replicates. Repeat these steps on at least two
other occasions with different operators and, where pos-
sible, different environmental conditions, for example,
different batches of reagents, standards and solvents.
Samples should be analysed, the identification criteria
1
The requirement that the substance must be identified (i.e. at least
the minimum number of IPs has been earned) as well as the require-
ment that its concentration exceeds CCα means that the certainty of the
decision is higher than the 99% claimed.
