Page 18 - January 2005 The Game

18 The Game, January 2005
Your Thoroughbred Racing Community Newspaper
HBPA Update
November 17 2004
Canadian Pari-Mutuel Agency (CPMA) Industry Workshop
Park Plaza Hotel, Toronto Airport, Toronto, Ontario, Canada, M9W 6H5
"Drug and Medication Testing Protocols"
by Thomas Tobin, The Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546
on behalf of the Horsemen's Benevolent and Protective Association of Canada and the Ontario Harness Horse Association
Executive Summary:
The Canadian Pari-Mutuel Agency testing program pioneered "limited sensitivity" testing for therapeutic medications. Canada is a leader in equine medication testing; today we respectfully suggest ways for Canada to maintain this position.
Urine testing is highly sensitive; it detects "traces" of medications long after their last administration; this is why urine testing is the basis of equine testing; it is also the reason for the limited sensitivity testing policy.
Another problem with urine testing is that it is inherently highly variable; blood testing now provides a substan- tial solution to these concerns.
We suggest that Canada build on it's in place policy by adding blood level quantification for therapeutic medications. LC-MS-MS analysis allows us to confidently confirm and quantify therapeutic medications in blood. Simply put, blood testing eliminates many of the problems associated with urine testing.
We therefore recommend pursuit of quantitative blood testing for therapeutic medications as the optimal approach to defining the forensic significance of residues of therapeutic medication.
Additionally, blood thresholds can readily be compared between jurisdictions, states and research data bases. This transferability compares very favorably with the current circumstance of three different booklets describing three different sets of withdrawal time guidelines in three different world regions (Australia, Canada and Europe). Quantitative blood testing will make such local systems a thing of the past.
We will also draw your attention to a blood threshold study on clenbuterol recently carried out in California. The number of horses used (19), the doses used, the analytical work and the analysis of yielded a well defined regulatory threshold in blood and
"withdrawal time guidelines" with use- ful error estimates. Data from studies of this type are immediately applicable worldwide.
In summary, quantitative blood test- ing is a forensically more reliable and, in human terms, a better and fairer way to regulate therapeutic medication than urine testing, which is inherently less satisfactory; on behalf of the Canadian HBPA and the Ontario HHA we are pleased to have the opportunity to recommend this approach to you.
1/ Background:
Let me start by thanking my Canadian colleagues for their contributions, in Lexington, 10 years ago, to the international workshop on "Testing for Therapeutic Medications, Environmental and Dietary Substances in Racing Horses" (1, 2). When Drs. Weber and Stevenson agreed to join the Lexington workshop and set forth how medication control was administered in Canada, I knew at once that the workshop was going to be a success.
2/ Limitations on the Sensitivity of Testing:
This workshop brought to the world the Canadian policy of "limits" on the sensitivity of testing for "therapeutic medications". The message of 10 years ago is just as valid today as it was then. What is changing is the best way to implement it.
3/ Urine Testing and Residues of Therapeutic Medications:
Urine testing has always been the basis of drug/medication testing; substances are found in urine in higher concentrations and for much longer times than in blood. Detection of improper administrations is the primary goal of equine drug testing, where urine testing is highly effective.
When, however, the goal is appropriate regulation of therapeutic medication, then the best solution is screening in urine, followed by quantitative blood testing to define the forensic significance of any findings.
In this regard, a major outcome of the 94 Workshop was two resolutions, adopted by the Association of Racing Commissioners International (ARCI) at the Oklahoma City meeting in 1995. These resolutions read as follows:
"The Association of Racing Commissioners International strongly recommends that its membership adopt a policy that all chemical findings in official test samples undergo a documented review process by the official veterinarian or appropriate
veterinary consultant prior to the initiation of any regulatory action".
"And, further, the ARCI recommends that its members specifically implement procedures to have an official veterinarian or veterinary consultant review findings for ARCI class 4 and 5 substances to address "trace" level detection so as not to lead to disciplinary action based on pharmacologically insignificant "traces" of these substances" our emphasis).
In adopting these resolutions, the ARCI specifically addressed the problem of basing administrative action on trace or insignificant levels of therapeutic substances in urine samples.
As will be detailed below, the times for which agents can be detected in urine are highly variable; the Australian Equine Veterinary Association (AEVA) notes that urine data provided in the AEVA booklet may GROSSLY UNDERESTIMATE [their emphasis and underlining] the maximum “detection time"
for some horses.
The solution to this problem is to move, where possible, to quantitative blood testing for therapeutic medications, as we will now set forth.
We also respectfully note that although the ARCI resolutions emphasize ARCI class 4 and 5 agents, therapeutic medications also include certain ARCI class 2 and 3 agents.
4/ Increased Capability of Blood Testing; Clenbuterol:
In 1998 we applied LC-MS-MS technology to blood testing for clenbuterol (3). The results showed that LC-MS-MS testing for clenbuterol in blood was highly sensitive and specific; we could test for and confirm down to 10 picograms/ml of clenbuterol in blood. This was a dramatic advance in the scope and sensitivity of blood testing.
Additionally, the regulatory approaches being evaluated by the Racing Medication Testing Consortium in the United States suggest an increased role for blood testing. In view of this, we will review the advantages of blood testing as compared with urine testing.
5/ Forensic Superiority of Blood Testing:
From a scientific point of view, all other things being equal, we have always known that on a theoretical basis, testing for therapeutic medications is likely to be much more satisfactory when carried out on blood
samples as compared with urine samples, for the following reasons:
5.1/ Blood Testing: Much less Variability in Analyte Concentration in Blood than in Urine:
The concentrations of drugs/medica- tions in blood samples vary much less than the concentrations found in urine.
This is because depending on the hydration status of the horse, the presence of diuretics, urinary pH and other factors, the concentrations of drugs/medications/ metabolites in equine urine can vary quite substan- tially. And when we say substantially, we mean 100 to 1,000 fold.
CPMA Industry Workshop- Drug & Medication Testing
5.2/ Blood Testing: Correlation between Concentration/ Pharmacological effect and Possible Time of Administration than in Urine.
The relationships between blood concentrations of drugs or medications and their pharmacological effects are reasonably well understood. As such, forensic data generated from blood samples are decidedly superior data for regulators to work with.
For a variety of reasons, the relation- ship between urine concentrations of drugs or drug metabolites and pharmacological effect is very difficult to decipher.
5.3/ Blood Testing: Avoids the Difficulties of Quantitatively Recovering and Analyzing Conjugated Urinary Metabolites:
The materials detected in blood are generally parent drug, and generally require no hydrolysis steps prior to recovery.
On the other hand, urinary metabolites are generally found in conjugated forms, from which the drug/metabolite has to be hydrolytically cleaved before it is recovered and analyzed, an added level of complication.
5.4/ Blood Testing: Analytical Standards Generally Available:
Blood testing generally detects parent drug; as such analytical standards are virtually always available (3, 4).
In urine testing, the material identified is often a unique metabolite and analytical standards are often not available, so accurate quantification is not possible (4).
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