Medication Control Programs in Performance Animals

Medication Control Programs in Performance Animals

Cynthia A. Cole

Regulation of Drug and Medication Use in Performance Animals

Horses, dogs, and other species frequently compete in athletic events in which the use of drugs and medications are controlled. The programs are often referred to as doping control: doping being the colloquial term for the illegitimate use of drugs to alter athletic performance in animals and man. The goals of medication control programs generally fall into three categories: (i) assure a fair and level playing field for the competitors, (ii) protect the health and welfare of the animal and human participants, and (iii) safeguard the public interest, whenever parimutuel wagering is involved. A major challenge in these programs is to control doping, but not to interfere with the legitimate use of veterinary medications. In addition, what is a medication in one setting could be seen as doping in another. For example, medicating a horse during the training phase to assist in healing from an injury is entirely legitimate, but administration of those same medications on race day, would likely be construed as doping (i.e., trying to make a sore horse sound enough to compete). Rarely is the differentiation between doping and appropriate veterinary care so obvious, however. For example, as laboratory methodologies have improved, it is now possible to detect some drugs days, weeks, or in some cases a month or more after they have been administered. This has led to the pivotal question of what is appropriate medical treatment of animal athletes. Treating a horse or dog during training is generally deemed acceptable, but residues of those medications can be detected long after they cease to have any demonstrable pharmacological activity. The difficulty in these situations is differentiating between a pharmacologically insignificant residue and one that may be associated with a pharmacological effect, even if that effect is small.

Overview of Regulatory Agencies and Stakeholder Organizations

It is important for veterinarians who treat animals that compete in events governed by medication control programs to understand that the regulatory environment is a dynamic one. What is permitted today in a program may be forbidden tomorrow. In addition, the sensitivity of the testing methods used to regulate compliance with medication rules continues to increase. As a result, the times required to discontinue the administration of medications prior to a competition in order to avoid positive tests, often referred to as withdrawal times, are also increasing. Veterinarians need to know what regulatory agency has authority over the events in which their clients are competing, so they can keep abreast of changes in medication rules and help their clients comply with them.

Racing Animals

Although there has been some discussion among industry stakeholders of the need for federal regulation, currently, medication rules for racing animals in the United States are determined by the individual states. States may have a Racing Commission, a Division of Parimutuel Wagering, or some other state agency that is given the authority and responsibility of regulating racing animals, horses and/or Greyhounds. It is the parimutuel wagering component of racing that has resulted in government oversight of these animal sports. Rules can vary significantly from state to state, so it is important to review the regulations in each state.

Although each state sets its own rules and regulations, there are several organizations that work to encourage harmonization of the programs. This is important because over a course of several weeks or months many horses may routinely race in several different states. The Association of Racing Commissioner’s International (ARCI) consists primarily of racing regulatory officials from the USA, Canada, and Caribbean ( It has no direct rule making authority, but the organization has developed model rules and penalty guidelines, which many states use as a framework for their regulations.

Another industry association is the Racing Medication and Testing Consortium (RMTC) the stated goals of which are to: develop and promote uniform rules, policies, and testing standards at the national level; coordinate research and educational programs that seek to ensure the integrity of racing and the health and welfare of racehorses and participants; and protect the interests of the racing public ( The organization consists of racing industry stakeholders and, similar to ARCI, it has no regulatory authority, but it does wield a great deal of influence. It has funded a significant amount of research related to drug and medication issues in racing horses and has developed a comprehensive Laboratory Code of Standards, as well as operating an External Quality Assurance Program. It also has developed withdrawal guidelines for many therapeutic substances and has worked closely with ARCI on model rules and a classification guideline for foreign substances.

In 1993 the International Federation of Horseracing Authorities (IFA), which has member countries around the world, was formed to: coordinate and harmonize the rules of the member countries regarding breeding, racing, and wagering, ensure the quality and fairness of racing, protect the welfare of horses, jockeys, and the people attending horseraces, and keep horseracing up to date with technical, social, and economic changes ( Its interests are broader in scope than either the RMTC or ARCI, which are more North American centric, but its influence in the North America is also less than those other organizations.

Nonracing Drug and Medication Rules

In the United States the largest governing body for drug and medication rules covering nonracing horses is the United States Equestrian Federation (USEF). A private, nongovernmental organization, the USEF regulates the vast majority of equine nonracing athletic events in the USA, including disciples recognized by the Federation Equestre International (FEI), which represents the most elite levels of equestrian competitions worldwide. The USEF has two rules under which the various breed groups and riding discipline organizations can choose to hold their competitions. Most breeds and disciplines that compete under USEF rules are subject to the Therapeutic Substance Provisions, which allows certain therapeutic medications to be present in clinically significant concentrations, while banning the presence of others outright. The Prohibited Substance Provisions rule, under which all FEI and Endurance competitions are conducted, classifies drugs as either controlled medications or banned substances. In this rule even controlled medications can only be present in nonpharmacologically significant concentrations, and therefore it is a much stricter rule than the Therapeutic Substance Provisions rule. The exact rules and regulations are updated frequently and details on both rules and advice on how to comply with them can be found on the USEF website (

The Drug Testing Process

In order to ensure compliance to drug and medication rules, biological samples are collected from animals participating in competitions either during or immediately after the event. There are a number of private and state run forensic drug testing laboratories that specialize in analyzing these samples for the presence of nonpermitted medications and overages of permitted, but controlled, medications. The testing process aims to separate and identify nonendogenous components or drugs in biological matrixes. The process can be separated into four steps: (i) sample collection, (ii) extraction, (iii) separation, and (iv) detection and identification.

Sample Type

Most commonly, urine and/or blood samples are collected and analyzed for the presence of nonpermitted substances and overages of permitted medications. Traditionally, urine has been used primarily for regulating nonpermitted substances, whereas blood samples were used to control permitted medications through adoption of regulatory limits or thresholds, but this approach is changing.

The selection of urine as the analytical matrix of choice is often made because it can be collected noninvasively with relative ease, particularly in horses. The large volumes typically voided in horses are also an advantage. In dogs, collection is a bit more difficult and volumes are often limited, but it is still the most common fluid collected in drug testing programs. Because many, if not most, drugs are eliminated in the urine and the kidney concentrates the urine, drugs can generally be detected in urine samples longer than they can be detected in blood samples. One limitation of the use of urine, however, is that it is very difficult to determine the pharmacological significance of the analytical finding, because urine concentrations will vary dramatically with the specific gravity of the urine.

Many medication control programs have been moving toward exclusively using blood samples, and the resulting serum or plasma collected from them, as the testing matrix. Even though, as previously mentioned, the concentration of drugs in the plasma/serum is often less than it is in urine, recent advances in technology have tremendously increased the sensitivity of analytical methods, generally rendering this disadvantage irrelevant. A major advantage of the use of plasma/serum harvested from blood samples is that the concentrations can more easily be correlated to pharmacodynamic effects if the relevant pharmacokinetic/pharmacodynamic studies have been conducted. A disadvantage to their use is the need for venipuncture, which is invasive and requires at the minimum a trained veterinary technician, if not a veterinarian.

Alternative matrixes, such as hair, have been investigated but their use is problematic. It would be extremely difficult to prove the time frame of exposure when a drug is found in a hair sample, and some horses may change hands several times in the course of the year. Saliva has also been used as a testing matrix, but because it is difficult to obtain sufficient volume to allow for a confirmatory analysis, its usefulness is limited.

Analytical Methods for Extraction

The goal of an extraction process is to isolate and concentrate the drug, referred to as an analyte, from the sample. One of the simplest and oldest extraction methods is a liquid–liquid extraction (LLE). In LLE a liquid biological matrix, such as urine or plasma, is mixed with an organic solvent that is not miscible with the sample. Most drugs are more soluble in the organic solvent than in the aqueous matrix of the sample, so they concentrate into the solvent during the mixing process. The solvent is separated from the aqueous phase and usually concentrated by evaporation to increase the concentration of the analyte in the final reconstitution buffer, which will increase the sensitivity of the assay. In solid-phase extraction (SPE) the organic matrix is passed through a column containing beads to which functional groups, such as hydrocarbons or ion exchange groups, have been bound. The analytes bind to the beads allowing the organic contaminants to be removed by washing the column. In the final step the column is buffered to a specific pH to facilitate release of the analytes, which are then removed from the column with a small amount of elution buffer. The buffer is generally removed by evaporation and the sample reconstituted in a solvent amendable to analysis. Analytes may also be extracted from the sample matrix by precipitation, which relies on differences in the solubility of the analytes and other compounds in the matrix. This process is commonly used to remove the proteins from plasma or serum, after which the resulting supernatant can be directly analyzed.

It is important to realize that different extraction processes may be more or less efficient at separating drug from the biological matrix. This can have significant regulatory ramifications because the final determination of the amount of drug present in the sample will depend to some extent on the extraction method used. So if two laboratories analyze the same sample using different extraction methods, the final concentrations of the analyte determined by the labs may be slightly different. The extraction efficiency is often determined during validation of an analytical method, but rarely is it factored into the determination of the final concentration in a biological sample.

Analytical Methods for Separation

The goal of the separation process is to isolate analytes from each other after extraction and prior to the detection process. The most common method used in forensic drug testing laboratories for the separation of analytes is chromatography. For a chromatographic separation the extracted sample is reconstituted in a mobile phase and passed through an immiscible stationary phase. Differences in the chemical characteristics of the analytes, such as polarity, size, and charge state, will cause them to have different rates of migration through the stationary phase. These differences, when optimized, result in the analytes moving through the column in discrete waves or bands, which can be collected or diverted to other instruments for further analysis.

One of the oldest types of chromatography is planar chromatography, where the stationary phase is bonded to a piece of glass or paper, and the mobile phase passes over it by either gravity or capillary action. Thin layer chromatography (TLC) is a type of planar chromatography that was used for many years in forensic drug testing laboratories as a primary screening test. Because it is possible for different analytes to have similar migration patterns, the findings are only presumptive and a second confirmatory method must always be employed. TLC is extremely labor intensive and not as sensitive as more modern chromatography methods, and therefore it is not used with much frequency today.

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Feb 8, 2018 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Medication Control Programs in Performance Animals

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