QA/QC measures

Under these conditions, it is obvious that the implementation of a QA/QC system is a strong requisite, along with a close and regular monitoring of the important components. This situation will engender a considerable use or consumption of the (C)RMs or QCMs.

The major components of this implementation follow.

5 Pesticide residue analysis.

4.2.1. Method validation

In order to validate the MRM⁶ to be used, working with representative commodities and representative analytes is a good option to extrapolate a great deal of analytes/matrices combinations.

The FAO/WHO CAC⁷ [59] organized food commodities in 33 groups, this classification can be reduced to fewer as presented in the Guidelines for Single-Laboratory Validation of Methods for Trace-Level Organic Chemicals [58], see Table XII.

In terms of analytes, especially if the number is very considerable and a grouping/classification is possible, the use of representative compounds for the QA/QC measures or the preparation of QCM should be explored.

This concept is applied for PRA and can be applicable in other analytical areas. Some representative compounds are shown in Table XIII for pesticides.

For veterinary drugs also, some practical guidance is given for the selection of appropriate matrix for testing, as shown in Table XIV.

TABLE XIII. SUMMARY OF PHYSICO-CHEMICAL PROPERTIES OF SELECTED REPRESENTATIVE COMPOUNDS

Water solubility Vapor pressure Hydrolysis Active ingredient

mg/l ^oC

LogPow⁸ at

pH and/or ^oC mPa at ^oC DT₅₀ [day] pH;^oC

DDE-p,p’ 0.065 24

Permethrin 0.2 30 6.1 at 20^oC 0.045 at 25^oC >720 4, 50 Endosulfan^a 0.32 22 4.74 at pH 5 0.83 at 25^aoC

Chlorothalonil 0.81 - 2.89 0.076 at 25^oC

Chlorpyrifos 1.4 20 4.7 2.7 at 25^oC In water, 1.5 8, 25

Lindane 7.3 25 5.6 at 20^oC 191 7, 22

Iprodione 13 20 3 at pH 3 & 5^oC 0.0005 at 25^oC 1 to7 7, -

Dimethoate 23.3 20 (pH 5) 0.704 1.1 at 25^oC 12 9, -

Azinphos-methyl 28 20 2.96 0.18 at 20^oC 87 4, 22

Diazinon 60 20 3.3 12 at 25^oC 0.49

185

3.1, 20 7.4, 20

Progargite 632 25 3.73 0.006 at 25^oC 800 7, -

Methamidophos 200,0 20 -0.8 at 20^oC 2.3 at 20^oC 657 4, 22

Note (a): 2:1 mixture of α and β isomers.

6 Multi-residue method.

7 Codex Alimentarius Commission.

8 Partition coefficient between n-octanol and water (as the log value).

TABLE XIV. APPROPRIATE TEST MATRIX FOR EXAMINATION OF RESIDUES OF VETERINARY DRUGS IN FOOD

Species/commodity for method

validation Usual target tissue or matrix for method validation

Water-soluble Fat soluble

Ruminant (e.g. cattle, sheep) Liver or kidney, muscle Fat, muscle Non-ruminant (e.g. pig) Liver or kidney, muscle Fat, muscle

Poultry (e.g. chicken, turkey)* Liver, muscle Fat, or muscle with adhering skin in normal proportions

Fish Muscle with adhering skin in

normal proportions

Muscle with adhering skin in normal proportions

Shellfish/crustacean (e.g. prawn) Muscle Muscle

Milk (usually cows’ milk) Whole milk Whole milk

Honey Honey Honey

In the validation process, use of the representative commodities and representative analytes concept would help to establish the basic characteristics of an analytical method.

At a later stage, appropriate internal QC measures shall be implemented. Moreover, refinement of the performance characteristics during the regular use of the method is an important internal QA measure.

Coming back to our scenario on the trace organic contaminants, applied methods are usually either validated and/or qualified as standard, official and reference methodologies. This condition fulfils an important QA criterion.

However, as the extent of validation is limited, use of CRMs is very pertinent.

In the case of repeated analyses of a CRM, the experimentally determined mean content should not deviate from the certified value more than ±10 %.

When no such (C)RMs are available, it is acceptable that the trueness of measurements is assessed through recovery of additions of known amounts of the analyte to the unknown or preferably blank samples. Attention is drawn to the fact that the added analyte is not chemically bound in the real matrix and therefore results obtained by this approach have lesser validity than those achieved through the use of natural matrix (C)RMs

Unfortunately, in this case the available CRMs do not match the need or do not exist at all.

Indeed, with respect to unstable matrices, such as foodstuffs, the matrix is often powdered and dried to ensure homogeneity and stability, creating finally a matrix mismatch.

Nevertheless, occasional check with the available (C)RMs (even if not matching), at or near either the maximum residue limit or decision limit, would deliver another proof for the goodness of the implemented QA/QC system.

4.2.2. Quality control

In order to compensate for the absence of (C)RMs and/or QCMs, the following basic QC steps are to be performed regularly and/or carried out simultaneously for each batch of test samples analysed:

– System suitability testing of the used instrument(s): to be performed first place

– Control charting for the principle parameters of the applied technique, e.g. recovery, yield, instrument performance and response

– Statistically sound acceptance criteria and evaluation of results

– Distribution of the reference substance (standard) over the whole analytical batch for the calibration

– Checking the calibration: use of two parameters: the coefficient of correlation (r) and the SD of (relative) residuals

– Analysis of blank samples to check interference: included in each analytical batch. Reagent blanks can be optional

– Recovery testing: included in each analytical batch

– Surrogate recovery testing⁹, if blank samples are not available

– Reference and fortified material containing known amounts of the analyte(s) as well as blank material should be treated in the same way as the test samples

– Qualitative and quantitative confirmation of measurand or residues detected above an action or acceptable level: each result

– Repeated analysis of positive samples: e.g. one in each analytical batch – Internal checks with blind samples in order to avoid the analysts’ bias

– Finally, some guidelines even give the recommended order for injecting the extracts into the analytical instrument, e.g. reagent blank, negative control sample, sample(s) being confirmed, negative control sample and finally positive control sample [60].

4.2.3. Additional quality control measures

Added to the points mentioned above, robustness or ruggedness of the analytical methods under different realistic conditions is a useful means to check the fitness for the purpose of the applied method. The variable conditions might be different sample weight, extraction solvent, detectors, wavelength, operators, etc.

With respect to the peculiar points of the instrument calibration [61] and the QCM preparation, use of a substance¹⁰ with certified purity as RM, is a must. As for recovery studies and spiking/fortification (whether for blanks or surrogates), they can be made using secondary standards¹¹ if the first choice is not possible and if secondary ones were certified against primary standards.

After viewing the essential internal QC measures, we can draw a limit between the advantages and drawbacks of usage of QCMs. Some of these are listed below:

Advantages:

(1) Provides consistent information on the performance of the method when applied for different samples of small numbers (as it is the best compromise. In case of large number of similar samples, a real matrix match RM is preferable);

(2) May be sufficient for QC of screening runs under certain conditions;

(3) Enables the application of control charts;

(4) Enables comparability between laboratories using the same materials.

Drawbacks:

(1) Not specific for the analyte/commodity combination analysed;

(2) Recovery studies with the tested combination are required for quantitative confirmation;

(3) Does not reveal, in general, information on the efficiency of sample processing (repeated analyses of test portions are still required).

Bearing these limitations in mind, we will present in the following section the relevant and feasible means of sample and analyte preservation leading to an appropriate and improved integrity of QCMs.

9 For more information about surrogates, check the ‘Harmonized Guidelines for the Use of recovery Information in Analytical Measurement (technical report)’ by M. Thompson, S. Ellison, A. Fajgelj, P. Willets and R. Wood, IUPAC, Pure Appl. Chem. 71 (1999) 337–348.

10 In the sense employed by the ISO Guide 11095.

11 With purity less than 95% or technical grade substance.