Specimen Validity Testing
Illicit drug use is defined as the use of marijuana, cocaine, heroin, hallucinogens, inhalants, or the non-medical use of prescription psychotherapeutics (prescription pain relievers, tranquilizers, stimulants, and sedatives). According to data released by the Substance Abuse and Mental Health Services Administration (SAMHSA) in 2012, nearly 23 million Americans aged 12 years or older participated in illicit drug use in the past month.1,2 That accounts for 8.7% of the population, making it a major public health problem in the United States.2
Urine drug screening is a clinical tool that can enhance workplace safety, monitor patients’ medication compliance, and detect drug (illicit and prescription) abuse as well as prescription medication diversion. Because drug testing is associated with personal, occupational, and legal implications, pain specialists and primary care physicians must be confident in their abilities to interpret urine drug assay results in order to respond duly to optimize clinical outcomes.3,4 When assessing for medication adherence, there are two areas of critical concern: one is the detection of a non-prescribed drug, an unexpected metabolite, or illicit substance; the other is a false-negative result. Adherence can be masked by dilute urine, quantity ingested, time since last dose, or the laboratory’s assay detection levels.3-5 Negative results in a dilute urine specimen may lead to misinterpretation of results. In situations where individuals attempt to evade detection of certain drug use, urinary substitution techniques and devices can be sophisticated and difficult to detect. The Internet offers a wealth of information regarding techniques to "pass" a standard drug test. These Internet sites provide everything from general advice to specific products designed to avoid drug detection in the user’s urine. There are basically three categories of such products: a) dilution and cleansing products, b) urine additives, and c) synthetic urine substitutes.4,5 In both the clinical setting and for federal workplace drug testing, the use of these methods to mask controlled substances in urine samples presents an ongoing challenge to drug screening.2,6,7 To counter these efforts, SAMHSA mandates the testing of creatinine, specific gravity (SG), and pH on all urine samples in order to verify specimen validity.5
Specimen validity testing is an important part of every urine drug test. It provides clinicians with critical information about the accuracy and reliability of drug test results, and that the specimen submitted is a valid human urine specimen. While specimen validity testing is not standardized with the use of in-office point-of-care drug testing, laboratories that specialize in urine drug testing often have established specimen validity testing protocols and toxicologists in place in order to assist with report interpretation.7 For the practitioner who has concerns regarding drug abuse or non-compliance, these specimen validity tests can also provide scientific results that, when coupled with other indicators (eg, incorrect pill counts, suspicious behaviors, clinical symptoms), may assist with the initiation of a conversation regarding potential drug abuse, mismanagement of medications, or diversion of prescribed drugs.
Creatinine is found naturally in the urine. It is produced by the breakdown of muscle tissue and cleared from the body via the kidneys. Creatinine is typically present between 20 and 400 mg/dL. A creatinine level outside of these values may result from excessive fluid intake, renal failure, diet, or a number of other medical conditions or factors.
SG is a measurement of the density of a liquid compared to the density of water. It measures the concentration of dissolved particles in the sample. Decreased SG values may be due to excessive fluid intake, renal failure, diabetes insipidus, as well as a variety of other factors. Increased SG values could be due to dehydration, renal dysfunction, and other medical factors including increased antidiuretic hormone secretion, which can be due to stress, trauma, and some drugs.8
The pH level determines the acidity or alkalinity of the sample. Urine pH values typically fall between 4.5 and 9.0. It is possible that urine specimen pH may be elevated up to 9.5 due to poor storage conditions such as elevated temperature.8 An extremely high or low pH can be an indication of tampering with a sample or adulteration.
Taken together, creatinine, SG, and pH are used to validate urine samples. All three of these important criteria must fall within the range of normal human urine for a urine sample to be considered valid. Categories of invalid samples are presented here.
Samples with a creatinine >2.0 and <20 mg/dL and an SG >1.0010 and <1.0030 are reported as dilute. A dilute specimen is a urine specimen with creatinine and SG values that are lower than expected for human urine.8 Dilution may be the result of many factors including ingestion of large amounts of water, a medical condition or medication, or adding water/liquid to a sample. The fact that a sample is dilute (for whatever reason) may impact the ability to detect any drugs present in the sample. Table 1 shows a report reflecting a dilute sample.
Samples with a creatinine <2.0 mg/dL and an SG <1.0010 and >1.0200 are reported as substituted. A substituted specimen is a urine specimen with creatinine and SG values that are so diminished or so divergent that they are not consistent with normal human urine.9
Samples with pH <3.0 or >11.0 are reported as adulterated. An adulterated specimen is a urine specimen containing a substance that is not a normal constituent of urine or a specimen containing an endogenous substance not present at a normal physiological concentration.9
Samples with a creatinine <2.0 mg/dL and an SG >1.0010 and <1.0200 or with a pH >9.0 but <11.0 are reported as invalid. A urine sample is classified as invalid when the creatinine and SG results are discrepant, or do not match, or when the pH is much lower or higher than typically expected. Table 2 shows a report of an invalid sample.
There are additional tests that may be performed in conjunction with the creatinine, SG, and pH specimen validity tests. A test for general oxidants or specific oxidants may be conducted to provide further information regarding the validity of a urine sample. Some common oxidants used to attempt to alter urine drug test results are bleach, nitrate, chromate, iodate, and peroxidase. A positive result for oxidant activity should be considered when interpreting drug results. Oxidants can cause decreased levels or negative results for certain drugs, either by masking the drug’s presence or by actually destroying the drug in the sample.