Analytical methods used for regulatory control of veterinary drug residues in foods of animal origin and their impacts on global trade

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Analytical methods used for regulatory control of
veterinary drug residues in foods of animal
origin and their impacts on global trade

• Joe Boison, Stephen Lee, Ron Gedir Johanna
  Chrusch
• CFIA Saskatoon Laboratory, Saskatoon, CANADA

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Location of the CFIA Laboratory in Saskatoon,
Saskatchewan, Canada
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Residue Monitoring and Control Program for
Veterinary Drug Residues

• Residue Plans Developed by the National Competent
  Authorities
• Domestic International Components
• Approved veterinary medicinal products with
  Acceptable Daily Intake (ADI)/MRL
• Approved veterinary medicinal products without
  ADI/MRL
• Approved veterinary medicinal products with
  Provisional Residue Limits
• Approved veterinary medicinal products used in
  extra-label fashion
• Unapproved/Prohibited veterinary medicinal
  products

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Veterinary Drug Classes included in Residue
Control Programs
Group Group Classification Examples of Drugs in Group
A1 Stilbenes Hexestrol, diethylstilboestrol, dienoestrol
A2 Thyreostats Thiouracil, tapazole
A3 Steroids boldenone, stanazalol, estradiol, trenbolone, dexamethasone
A4 Resorcylic acid lactones Zeranol
A5 Beta agonists Cimaterol, salbutamol, mabuterol, ractopamine, clenbuterol
A6 Prohibited compounds chloramphenicol
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Veterinary Drug Classes included in Residue
Control Programs
Group Classification Examples
B2a Anthelmintics
Benzimidazoles Triclabendazole, albendazole, oxfendazole, fenbendazole
Imidazothiazoles Levamisole
Salicylanilides Closantel
Macrocyclic lactones Abamectin, doramectin, emamectin, eprinomectin, ivermectin
B2c Carbamates Chlorfluazuron, diflubenzuron, fluazuron
Pyrethroids Cyfluthrin, cyhalothrin, cypermethrin fenvalerate
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Veterinary Drug Classes included in Residue
Control Programs
Group Classification Examples
B2e NSAIDs Flunixin, ketoprofen, phenylbutazone, oxyphenbutazone, tolfenamic acid
B3a Organochlorines Aldrin/dieldrin, DDT metabolites, PCBs
B3b Organophosphates Chlorpyrifos, coumaphos, diazinon, phosmet
B3e Heavy metals Cadmium, lead, mercury
B3d Mycotoxins Zearalenone, a-zearalenol, ß-zearalenol
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Unauthorised Substances in Bovine Livers
Drug Matrix AUS CAC CDA EU USA JPN
Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg) Corticosteroids (Group A3) MRL (mg/kg)
Dexamethasone L - .002 P - 0.002 - 0.004 P
Betamethasone L 0.1 (eo) - - 0.002 - 0.002 P
Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg Resorcylic acid lactones (Group A4) MRL mg/kg
Zeranol L 0.02 (eo) 0.01 0.01 - Not needed 0.01
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Unauthorised Substances in Bovine Liver
Drug Matrix Matrix AUS AUS CAC CAC CDA CDA EU USA JPN
Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg) Beta-agonists (Group A5) MRL (mg/kg)
Cimaterol L - - - - - - 0.002 0.002 - 0.004P
Mabuterol L - - - - - - - - -
Ractopamine L 0.1 K 0.1 K 0.04 0.04 0.04 0.04 NS NS 0.015 0.04
Clenbuterol L 0.1 (eo) 0.1 (eo) 0.0006 0.0006 0.002 0.002 - 0.002P
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Japans Positive List Substances that are
stipulated to be Not detected in foods

1. 2,4,5-T
2. Amitrole
3. Azocyclotin cyhexatin
4. Captafol
5. Carbadox
6. Chloramphenicol
7. Chlorpromazine
8. Coumaphos
9. Daminozide
10. Diestylstilbesterol

• Dimetridazole
• Furaltadone
• Furazolidone
• Malachite green
• Metronidazole
• Nitrofurantoin
• Nitrofurazone
• Propham
• Ronidazole
• Updated Nov 6, 2008

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Chemical Structures of Compounds on Japans
Positive List
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Chemical Structures of Compounds on Japans
Positive List
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Residue Monitoring and Control Program and
International Trade

• Codex Alimentarius Committee (CAC) administers
  the FAO/WHO Food Standards Program for food of
  animal origin which includes meat and meat
  products, milk and milk products, eggs and egg
  products, and products of aquatic animals derived
  from aquaculture
• JMPR - Joint FAO/WHO Committee on Pesticide
  Residues
• JECFA Joint FAO/WHO Expert Committee on Food
  Additives

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Residue Monitoring and Control Program
International Trade (SPS TBT)

• The Uruguay round of Multilateral Trade
  Negotiations established the WTO to reduce
  non-tariff barriers to international trade.
• Agreement on Sanitary and Phytosanitary (SPS)
  Measures
• Agreement on Technical Barriers to Trade (TBT)

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The SPS Agreement

• The SPS Agreement confirms the right of WTO
  Member countries to apply measures to protect
  human, animal and plant life and health
• provided that such measures are not applied in a
  manner which would constitute a means of
  arbitrary or unjustifiable discrimination between
  countries where the same conditions prevail, or a
  disguised restriction on international trade.
• References the standards, guidelines,
  recommendations established by the CAC relating
  to food additives, residues of veterinary drugs
  and pesticides, contaminants
• methods of sampling and analysis and
• codes and guidelines of hygienic practice.

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The SPS

• Provides Measures to ensure
• adherence in food of animal origin to the Codex
  maximum levels or guideline levels for
  contaminants, and to the Codex maximum residue
  limits (MRLs) for pesticide and veterinary drugs.
• that appropriate hygienic practices are followed
  at all stages of animal feeding chain to prevent,
  eliminate, or reduce potential hazards in the
  food.

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The TBT Agreement

• Objective is prevent the use of national or
  regional technical requirements, or standards in
  general, as unjustified technical barriers to
  trade.
• It covers all kinds of
• Food standards other than those related to the
  SPS measures
• Measures designed to protect the consumer against
  deception and economic fraud
• Quality provisions
• Nutritional requirements
• Labelling and
• Methods of analysis.

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The TBT Agreement

• It provides that
• All the technical requirements and regulations
  must have a legitimate purpose
• The impact or cost of implementing the measure
  must be proportional to the purpose of the
  measure
• Emphasis be placed on international standards.

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Veterinary Drugs

• Only veterinary medicinal products licensed for
  administration to food producing animals should
  be used and the withholding time should be
  observed/respected before milk or eggs are used
  for food or animals are sent for slaughter,
• Adherence to the Codex Code of Practice and
  Guidelines for Control of and use of Veterinary
  Drugs and of Veterinary Drug Residues in Foods to
  ensure that animal feeds do not contribute to
  excessive veterinary drug residues in foods.

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Japan, Canada and Codex MRLs for Ractopamine
Residues in Edible Animal Tissues
Matrix JPN (mg/kg) JPN (mg/kg) CDA (mg/kg) CDA (mg/kg) CAC(mg/kg) CAC(mg/kg)
Matrix Bovine Porcine Bovine Porcine Bovine Porcine
Muscle 0.01 0.01 0.01 0.04 0.01 0.01
Kidney 0.09 0.09 0.10 0.14 0.09 0.09
Liver 0.04 0.04 0.04 0.12 0.04 0.04
Fat 0.01 0.01 - - 0.01 0.01
Edible offal 0.04 0.04 - - - -
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2695 Alliance LC with a Diode Array Detector
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2695 Alliance ZQ Single Quadrupole MS
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Acquity UPLC Triple Quadrupole MS Detector
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Quantitative LC-MS Analysis of Colistin B
Residues in Chicken Muscle Tissue
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Quantitative LC-MS Analysis of Enduracidin A
Residues in Chicken Muscle Tissue
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Quattro Ultima Triple Quadrupole MS
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Alliance Quattro Micro Triple Quadrupole MS
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Acquity UPLC Quattro Premier Triple Quadrupole MS
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Chemical Structure of Bacitracin A
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Mass Spectrum of Bacitracin A
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Confirmatory Analysis by LC-Tandem Mass
Spectrometry (LC-MS/MS)
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Acquity UPLC SYNAPT Quadrupole Time Of Flight MS
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Acknowledgement

• Johanna Chrusch
• Stephen Lee
• Ron Gedir

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