Minimum required performance limit

Minimum required performance limits have been established for substances for which no permitted limit has been fixed and in particular for those substances whose use is not authorized or even prohibited within the EU (group A). A MRPL is the minimum content of an analyte in a sample which at least has to be detected and confirmed. A few MRPLs for residues of certain veterinary drugs have been published so far in directive 2003/181/EC. 

European Commission (EC), Commission decision 2003/181/EC amending decision 2002/657/EC as regards the setting of minimum required performance limits (MRPLs) for certain residues in food of animal origin, Off. J. Eur. Commun., L 71/17, 0017-0018, 15.3.2003. 

The analysis of the broad-spectram antibiotics chloramphenicol (CAP) has recently attained considerable attention. CAP has been used to treat food-producing animals from the 1950s until it was harmed by the EU in 1994. The minimum required performance limit for analytical methods for CAP within the EU is 2 pg/kg. 

Within the EU, in contrast with other areas of food control, there is no obligation to use standardized methods in the surveillance of veterinary medicine residues. Instead, a criterion-based approach applies that defines the performance characteristics that the methods used must meet." However, within the United States and some other countries methods are statutorily prescribed. The method must be able to detect the marker residue, specifically, mefabolife, sum of metabolites, or parent compound at/or below the appropriate regulatory limit (RL), as available. In the EU, the RL for authorized veterinary medicinal products is the maximum residue limit (MRL). The RL for prohibited and unauthorized substances is the minimum required performance limit (MRPL) or the reference point for action (RPA). ° In other cases, especially for unauthorized substances, the Community Reference Laboratory (CRL) Recommended Concentration (RC)" can be applied, although this has no legal standing and is not a limit per se. 

MRLs or required method validation concentrations can be different for various residues. It may not be practical to quantify all antibiotics of interest in the same analytical range, if it is required. The analytical ranges for quantification are usually based on MRLs, the minimum required performance limit (MRPL) concentration, or a required method validation concentration. LC-MS typically has a linear or quadratic dynamic range of 2-3 orders of magnitude, and some antibiotics demonstrate better linear response than others. In general, it may be possible... 

Thiamphenicol and fiorfenicol, which have structures similar to that of CAP (Fig. 7.3), are permitted as substitutes within the EU." " In the EU, MRLs for thiamphenicol are 50 p-g/kg for bovine and chicken tissues, and for fiorfenicol, 100 pg/kg for muscle to 3000 pg/kg for bovine liver. Within the EU fiorfenicol also has a complex MRL definition, and this will be discussed in Section 7.9.2.1. Because of the ban on CAP, methods with very low detection limits have been developed. A minimum required performance limit (MRPL) of 0.3 pg/kg was assigned by the European Commission for the analytical methods testing for CAP in products of animal origin." ... 

Prepare a set of samples of specified test material (identical or different matrices), fortified with the analyte(s) to yield concentrations equivalent to 1, 1.5, and 2 times the minimum required performance limit or 0.5, 1, and 1.5 times the permitted limit. 

A major factor affecting the quality of the final result is the suitability of the analytical method applied. Ensuring that the method is fit for purpose can be considered a basic quality control criterion. It is important that laboratories restrict their choice of methods to those that have been characterized as suitable for the matrix and analyte of interest, and at the level of interest. In the EU, and in many other countries and regions, the regulatory limit for authorized veterinary medicinal products is the maximum residue limit (MRL), and for contaminants the maximum permitted limit. Eor prohibited or unauthorized analytes, there is often a threshold or action limit set in Europe, for example, the appropriate regulatory limit is the minimum required performance limit (MRPL) or the reference point for action (RPA), as defined in Article 4 of Commission Decision 2002/657/EC, Article 2 of Commission Decision 2005/34/EC, and Articles 18 and 19 of Council Regulation (EEC) 470/2009.2 ... 

Methods are validated using samples fortified with the analyte of interest at appropriate levels (i.e., normally levels similar to levels found in the samples), levels related to MRLs for permitted substances, or levels related to minimum required performance limits for prohibited or unapproved substances. Following validation of the method and its... 

Commission Decision 2002/657/EC [12] defines the performance criteria for analytical residue methods and is probably the key document of legislation to be consulted by residue control laboratories. This reference document introduces the concept of the minimum required performance limit (MRPL) for compounds belonging to Group A it corresponds to the minimum content of an analyte in a sample that has to be detected and confirmed, and it constitutes the lowest level that can be reliably considered "nonzero."... 

Several of these assays are still in use in various fields of analytical chemistry but usually not in sports drug testing, where comprehensive, fast, and specific procedures are required. Although detection limits of numerous methods would fulfill so-called minimum required performance limits as established by WADA, the inferior specificity of UV-spectra compared to mass spectrometric information has led to several endeavors to combine the liquid chromatographic separation units via ionization interfaces to all kinds of mass spectrometers. 

The detection and identification of prohibited compounds and methods of doping has been regulated for sports drug testing laboratories particularly by guidelines established by the IOC and, since 2001, the WADA/ Respective technical documents were created that outlined minimum required performance limits as well as international standards for laboratories (ISL), which accredited doping control laboratories must follow as evaluated in one or more annually conducted proficiency test programs. 

World Anti-Doping Agency (2009) Minimum Required Performance Limits for DetectionofProhibitedSubstances.A ailableathttp ll mv/.w iMINIMUM REQUIRED PERFORMANCE LEVELS TD vl 0 January 2009.pd Accessed 11-24-2008. 

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