Veterinary drug residues, determination

V. Lopez-AvUa and J. Benedicto, Determination of veterinary drugs in dry milk powder by supercritical fluid extraction-enzyme hnked immunosorbent assay, in Veterinary Drug Residues Food Safety, ed. W.A. Moats and M.B. Medina, American Chemical Society, Washington, DC, Chapter 15, pp. 145-148 (1995). 

According to Directive 86/469/EEC of 16 September, 1986 (49), and its amendments, each Member State is required to test for the presence of antibiotics and other veterinary drug residues in edible animal products. Under the EU Annual National Plan (ANP) program, each Member State has to submit every year to the Commission a monitoring plan taking into account the specific national situation and setting out the national measures to be taken. The Commission examines the plans communicated by Member States to determine if they conform to the provisions laid down by Directive 86/469/EEC. 

Chemical analytical methods used in veterinary drug residue depletion studies in target animals constitute a potential source of suitable methods for determining compliance of tissue residues with established MRLs. In some situations. 

More recent surveillance indicates that the incidence of veterinary drug residues above MRLs is falling. Results from the 1994 UK surveillance programs showed that a total of approximately 0.2% of all samples analyzed contained violative residues (31). By way of comparison, the total in excess of MRLs in 1993 was also 0.2%, whereas in 1992 the figure was 0.48%. A total of 5 of 86 samples of imported swine kidney contained residues of tetracyclines in excess of the MRL. Apart from tetracyclines, 1.7% of the swine kidney samples were found to contain residues of sulfonamides above the MRL, compared with 1.5% in 1993. This is likely to have resulted from the increased use of sulfonamides to treat respiratory disease. Residues of nicarbazin were determined in 8 samples, residues of sulfonamides in 11 samples, and residues of lasalocid in 46 of the 429 egg samples analyzed. One sample contained residues of sulfadiazine at a level of 924 ppb. 

The most recently reported UK results on surveillance for veterinary drug residues in meat and animal products show that traces of these compounds can, and sometimes do, arise in food. As all of these compounds are biologically potent in order to be effective in use, it is necessary to ensure that any residual activity in a food product does not present a risk to the consumer. The use of veterinary medicines inevitably leads to the presence of trace residues in food and the purpose of toxicological safety evaluation is to determine at what concentration the residues of a particular compound becomes a cause for concern with regard to human health. Thus, dose-response relationships have to be established and used to determine the concentration of a dmg at which the risks to human health become acceptable and are outweighed by the benefits from the use of the drug. This is in essence the process involved in the setting of Acceptable Daily Intakes (ADIs) and... 

Considering methods of sampling and analysis for the determination of veterinary drug residues in foods. 

Harris, J. Wilkins, J. The Application of HPLC-Cone Voltage Assisted Fragmentation Electrospray Mass Spectrometry to the Determination of Veterinary Drug Residues. In Residues of Veterinary Drugs in Food, Proceedings of the Euroresidue III Conference, Veldhoven, May 6-8, 1996 Haagsma, N., Ruiter, A., Eds. Fac. Vet. Med., Univ. Utrecht The Netherlands, 1996. 

Ultra-high-performance liquid chromatography has been increasingly used for the determination of multi-residue or multi-class antibiotics in food (Table 6.1). For example, an UHPLC/ESI-MS/MS method was reported to simultaneously analyze 17 different veterinary drug residues belonging to several classes of antibiotics such as macrolides, tetracyclines, quinolones, and sulfonamides... 

In 2009, the CAC approved a new guideline for the validation of methods used for the determination of veterinary drug residues in foods (CAC/GL 71-2009), which replaced the previous guidance. The new guidance states that methods may be validated in a single laboratory, provided that the validation meets the General Criteria for the Selection of Methods of Analysis contained in the CAC Procedural Manual In addition ... 

The use of pre-extraction spiking is particularly important when the presence of matrix co-extractives modifies the response of the analyte as compared with analytical standards. It is increasingly common in methods for veterinary drug residues in foods to base the quantitative determination on a standard curve prepared by addition of standard to known blank representative matrix material at a range of appropriate concentrations that bracket the target value (the analytical function). Use of such a tissue standard curve for calibration incorporates a recovery correction into the analytical results obtained. 

Analytical results for the determination of antibiotic residues in food, in common with results generated in other laboratories or branches of analytical chemistry, must be reliable and comparable. It is a requirement for laboratories accredited under the ISO/IEC 17025 quality system that the measurement uncertainty associated with a result should be made available and reported if it is required by the client, is relevant to the validity of the test results, or may affect compliance with a specification, for example, compliance with a maximum residue limit (MRL) for antibiotics. The Codex Alimentarius Commission also recommends that laboratories provide their customers on request with information on the measurement uncertainty or a statement of confidence associated with quantitative results for veterinary drug residues. The relevant sections in ISO 17025 are quoted below ... 

It can be assumed that with the development and study of new methods, the ability to determine M (S), the method bias component of uncertainty, cannot be done given that it can be evaluated only relative to a true measure of analyte concentration. This can be achieved by analysis of a certified reference material, which is usually uncommon, or by comparison to a well-characterized/accepted method, which is unlikely to exist for veterinary drug residues of recent interest. Given that method bias is typically corrected using matrix-matched calibration standards, internal standard or recovery spikes, it is considered that the use of these approaches provides correction for the systematic component of method bias. The random error would be considered part of the interlaboratory derived components of uncertainty. 

Tetracyclines, nonsteroidal anti-inflammatory, antidepressants, " and mixtures of acidic drugs as well as veterinary drug residues have been determined by CZE (citric acid/citrate, borate, borate in MeOH, phosphate/MeOH, ammonium formate/formic acid/ACN, ammonium acetate, ammonium acetate/acetic acid/MeOH) and EKC (SDS/pH 2.5 phosphate buffer/ACN) methodologies in water samples from influent and effluent of sewage treatment plants as well as wastewater, river, surface and groundwater as compiled in Table 31.9. Estrogens have been receiving increased attention due to the already mentioned possible interference with the reproductive... 

Jafari, M.T. Khayamian, T. Shaer, V. Zarei, N., Determination of veterinary drug residues in chicken meat nsing corona discharge ion mobility spectrometry. Anal. Chim. 

There have been major developments in LC coupled with MS (LC-MS/MS) during the last 5-10 years and this technology has been applied very widely for veterinary drug residue analysis (Figure 4). LC-MS/MS is particularly suitable for veterinary drug residues in that derivatization, commonly required for GC-MS analysis, is not necessary. In addition, it can provide robust and sensitive determination. 

Another source of concern in food safety control is the increasing amounts of residues of veterinary drugs that can be found in foods. These drugs are mostly antibiotics of different structures, such as tetracyclines, macrolides, quinolones, sulphona-mides, and 6-lactams. The preferred analytical technique for antibiotic residue determination is HPLC, and specific methods for each family of antibiotics can be fovmd in the scientific literature. Most of the published methods use RP columns with gradient elution. Every available detection method can be used, depending on the application, though MS is a powerful technique for the identification and confirmation of veterinary drug residues in food samples, and at the moment, LC-MS is the method of reference. 

Harris, J. Wilkins, J. The appUcation of HPLC one voltage assisted fragmentation electrospray mass spectrometry to the determination of veterinary drug residues. In... 

Balizs, G. and Hewitt, A. (2003) Determination of veterinary drug residues by liquid chromatography and tandem mass spectrometry. Analytica Chimica Acta 492,105-131. 

Determination of Veterinary Drug Residues in Foods by Liquid Chromatography—Mass Spectrometry Basic and Cutting-Edge Applications... 

TABLE 17.2 Summary of Representative LC—MS/MS Methods for the Determination of Target Veterinary Drug Residues in Food Samples... 

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