Target residue validation method

ID target residues have been measured in wastewater samples with fully validated, highly selective multiresidue assays. Briefly, water samples were generally sohd-phase extracted, purified, and subsequerrtly analyzed by hqtrid chromatograplty— tandem mass spectrometry or alternative methods. These methods are reviewed elsewhere in this book (see Chapter 3). 

The use of common moiety methods acceptable in exceptional circumstances where there is no other practical means of determining the target analyte, and in these cases, full justification is required. This should include an explanation of why the compound cannot be determined by a specific analytical technique. For existing a.i., common moiety methods are also acceptable, in cases where the residue definition includes a common moiety. Moreover, validation data must be presented separately for all relevant components. 

The workhorses in national monitoring programs are multi-residue methods. Any official method collection of any EU Member State contains at least one multi-residue method. For multi-analyte and/or multi-matrix methods, it is likely to be impractical to validate a method for all possible combinations of analyte, concentration and type of sample matrix that may be encountered in subsequent use of the method. Therefore, initial validation should incorporate as many of the target analytes and matrices as practicable. For practical reasons this validation and the evaluation of other methods with limited scope often cannot be conducted in inter-laboratory studies. Other concepts based on independent laboratory validation or validation in a single laboratory have been developed and can provide a practical and cost-effective alternative (or intermediate) approach. 

Several considerations influence the suitability of the immunoassay as a qualitative or quantitative tool for the determination of tissue residues. These include the assay format, the end user (on-farm or laboratory use), effects of sample matrix on the analysis, cross-reactivity considerations, detection levels required of the assay, target tissues to be used in the assay, and the use of incurred or fortified tissues for validation of the immunoassay against accepted instrumental methods. Although these variables are often interrelated, each topic will be discussed in further detail below. 

Up to now there has been no calculation of differential cross sections by a method that is generally valid. We use a formulation due to Konovalov (1993). Understanding of ionisation has advanced by an iterative process involving experiments and calculations that emphasise different aspects of the reaction. Kinematic regions have been found that are completely understood in the sense that absolute differential cross sections in detailed agreement with experiment can be calculated. These form the basis of a structure probe, electron momentum spectroscopy, that is extremely sensitive to one-electron and electron-correlation properties of the target ground state and observed states of the residual ion. It forms a test of unprecedented scope and sensitivity for structure calculations that is described in chapter 11. 

Detciils of impurities shall be provided (i.e., residues of starting materials, solvents, by products of breakdown products) when stating which impurities are likely to occur and methods used to detect their presence. It must be indicated whether such impurities occur in normal production and in what quantities, supported by analytical results of a number of batches. Validation of important production processes emd reports must be submitted. The specifications and grades of raw materials used are to be provided as well as target specifications, punch sizes and hcirdness limits where applicable. All limits determinations and specifications for the finished products must be provided. Packaging/filling instruction may also be required. 

Several groups have adapted the method to analyze residues in a variety of matrices. Acetic acid (HQAc, 1%) and sodium acetate have been widely used to adjust and maintain pH and promote stability and recovery of base-sensitive residues. HOAc was used to adjust pH by Stubbings and Bigwood to determine residues [sulfonamides, quinolones, (fluoro)quinolones, ionophores, and nitroimidazoles] in chicken muscle. Buffering to acidic conditions improved the extraction efficiency of quinolones. Aeetonitrile extracts were subsequently purified by dSPE (see also Section 4.4.6.1) over Bondesil NH2 sorbent. An aliquot of the extracts was evaporated to dryness and re-dissolved in acetonitrile water (90 10, v/v) before LC-MS/MS analysis. Validation was performed on chicken muscle samples, and matrix-matched standards were used because suppression of the MS response was observed for many of the target analytes. 

Any other factors that may define the analytical requirements should also be considered. For example, when dealing with veterinary drug residue analysis, while the target tissue for domestically produced animals may be liver or kidney, these organ tissues are less commonly available as imported products. The majority of imported meat products are muscle tissue. Therefore, although the method has been validated for analysis of kidney for domestic samples, it is not fit for purpose for use on most import samples until it has also been validated for muscle tissue and possibly even some processed meat products. A method validated for the analysis of an aquaculture drug or natural toxin in oysters from domestic production may also, for example, require validation for shrimp or tilapia for application to imports. In addition, the requirement may include development of a... 

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