CLN Article

Developing Standards for Oral Fluid as an Alternative Matrix for Toxicology Testing

Ronald R. Flegel, MT(ASCP), MS, and Carolyn Humbert, MA

The Substance Abuse and Mental Health Services Administration (SAMHSA), part of the Department of Health and Human Services (HHS), publishes the scientific and technical guidelines for federal workplace drug-testing programs. Current mandatory guidelines require immunoassay for initial drug testing and combined chromatographic/mass spectrometric methods for confirmatory drug testing. In addition, urine is the only testing matrix currently approved for federal drug testing.

However, HHS is taking steps to expand approved testing matrices. In particular, the scientific basis for oral fluid as an alternative specimen for drug testing has now been established broadly. For example, oral fluid collection devices and procedures have been developed that protect against biohazards, maintain the stability of analytes, and provide sufficient oral fluid for testing. In addition, current analyte cutoff concentrations are much lower than those specified for urine drug testing.

HHS has proposed mandatory guidelines for urine and oral fluid that would allow immunoassay or alternate technologies for initial drug testing (1). Alternate technologies include three different mass spectrometry techniques: gas chromatography/mass spectrometry (GC/MS), liquid chromatography-mass spectrometry (LC-MS), and gas/liquid chromatography tandem mass spectrometry (GC-MS/MS, LC-MS/MS).  Of the three techniques, LC-MS/MS should be the primary analytical method for drug testing matrices.

Key features in establishing the federal government’s oral fluid testing program included ensuring proper performance of collection device(s), incorporating new technologies, establishing a knowledge base for interpreting results, collecting a second (“split”) oral fluid specimen that can be used for confirming the initial laboratory result, and selecting cutoff concentrations, including for synthetic opiates (See Table) (1).

Proposed Cutoff Concentrations for Oral Fluid

The proposed guidelines define oral fluid as the physiological fluid that can be collected from the oral cavity of the mouth. It’s important to note that although saliva is the main constituent of oral fluid, other sources contribute as well, including minor salivary glands, fluid from between the gums and teeth, cellular debris, bacteria, and food residues. Similarly, while oral fluid consists mainly of water, it also includes electrolytes such as potassium, sodium, chloride, bicarbonates, and phosphates, as well as organic substances such as enzymes, immunoglobulins, and mucins.

As has been the case with previous mandatory guidelines, the oral fluid standards HHS develops for the federal government might be adopted or modified to meet program requirements for non-federally regulated drug testing programs, private companies, and clinical settings. These standards are especially important in driving under the influence of drugs (DUID) investigations. Establishing cutoff concentrations is crucial for law enforcement, but will encompass additional considerations beyond those in federal workplace drug testing (1).

Enhanced Flexibility and Reduced Costs

A key benefit of oral fluid as an alternative testing matrix is its flexibility to meet various workplace drug testing needs. For example, certain medical conditions may prevent employees or applicants from providing sufficient urine for a drug test. If an employer were permitted to collect an oral fluid specimen instead of urine, doing so would reduce both the need to reschedule collections and for the medical review officer to medically evaluate a donor’s inability to provide a specimen.

Similarly, oral fluid can be collected in a wide variety of settings, unlike urine collection that requires a specialized collection facility, secured restrooms, a collector of the same sex as the individual providing the sample, and other special requirements. An acceptable oral fluid collection site requires that the collector observe the donor, maintain control of the collection device(s) during the process, maintain record storage, and protect donor privacy. With lower expenses for oral fluid shipping and storage, and less time required of the donor for the collection process, it also saves employers money. 

In addition, oral fluid reduces any opportunity a donor might have to adulterate or substitute a specimen because the collector is able to observe the donor and maintain control of the collection device during the process. Under the proposed guidelines, specimen validity testing of oral fluid will be allowed using albumin or immunoglobulin G to determine whether the specimen is consistent with normal human oral fluid (1).

Detection Versatility

The time course of drugs and metabolites differs between oral fluid and urine, resulting in different analytes and variable detection times. Oral fluid tests generally are positive as soon as the drug is absorbed into the body. In contrast, urine tests based solely on detecting a metabolite are dependent upon the rate and extent of metabolite formation. Consequently, oral fluid may offer more interpretative insight into drug use and impaired behavior at the time the specimen is collected.

Public as well as private organizations that test their employees may select the specimen type based on the circumstances of the test. This is paramount to organizations that carry out fitness for duty programs. For example, there may be strong interest in testing for semi-synthetic opioids (such as oxycodone and hydrocodone), or in situations of suspected worksite drug use. Oral fluid testing may show the presence of an active drug, which may indicate recent administration of the drug, and it may be advantageous when assessing whether the drug contributed to an observed behavior (1). Note that the proposed guideline would not allow employers to collect both urine and oral fluid during the same collection event.

Next Steps

Laboratory-based testing technology has advanced to a point where the limitations of volume and sensitivity are no longer major barriers to routine oral fluid analyses. With these advances in technology, oral fluid testing has gained acceptance in forensic settings such as workplaces, sports, pain management, and roadside testing for DUID. The proposed draft of the Mandatory Guidelines for Federal Workplace Drug Testing Programs takes the first step toward establishing a set of standards for oral fluid testing in a regulated testing program. Standards for collection devices and technical requirements for federal workplace drug testing would mean that non-regulated entities, private companies, clinical program settings, and possibly federal and state law enforcement agencies looking to establish programs for roadside impairment testing also will be able to reliably use oral fluid testing.

A focus of the HHS mission is to ensure the integrity of a federal drug-free workplace program through identifying and mandating the use of the most accurate, reliable drug tests and methods. HHS through SAMHSA’s Drug Testing Advisory Board (DTAB) also has been proactively responding in light of increasing use of oral fluid as part of an alternative drug testing matrix, commercial products now available for oral fluid collection, and advances in analytical testing technologies for oral fluid specimens. DTAB has implemented extensive ongoing scientific reviews, which have included program collaboration with federal regulators, researchers, the drug testing industry, and input from the public. The goal of these efforts has been to assess new products and analytical testing technologies so as to advance federal workplace safety as mandated through the federal government’s federal workplace drug testing program (1).

For more information on current and proposed guidelines and to read the Federal Register notices, visit the SAMHSA website,

Ronald R. Flegel, MS, MT(ASCP), is director of the Division of Workplace Programs in the Center for Substance Abuse Prevention in the Substance Abuse and Mental Health Services Administration, part of the Department of Health and Human Services. +Email: [email protected]


1. Department of Health and Human Services. Proposed mandatory guidelines for federal workplace drug testing programs – Oral fluid (94 FR 28054 - May 15, 2015). (Accessed September 2017).

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