The Responses Of Laboratory and Regulatory Agency to the Problem

Characteristics of Human Urine

The human urine characteristics can vary extensively among individuals. Urine characteristics are affected by factors such as an individual’s diet, fluid intake and condition of health, metabolic differences, physical condition and gender. Urine is an aqueous solution with fluctuating amounts of electrolytes, metabolic products, and other products of human elimination. It has long been characterized by its physical individuality of color, clarity, and odor. Fresh random urine should be straw-colored, clear, and odorless. In dealing with their testing programs, the US Department of Defense has gone so far as to publish a review of the characterization of urine. Tests to distinguish adulterated, dilute, substituted, or invalid specimens from valid urine samples in workplace drug testing programs are referred to as “Specimen Validity Tests” (SVTs). Creatinine, definite gravity pit, and oxidant activity tests are the Slots performed to evaluate whether the characteristics of the urine sample are constant with expected values for human urine. The HHS Mandatory Guidelines specify the acceptable ranges for urine creatinine, specific gravity, pH, and oxidant activity test results for federally regulated drug-testing samples.

Creatinine is a waste product of creatinine in skeletal muscle. Because the amount of creatinine produced every day is comparatively steady, renal clearance of creatinine is used in clinical applications to estimate the glomerular filtration rate (GFR), which is in turn used to assess kidney function. Urine detailed gravity is tee density of urine compared to the density of water at the same temperature. Specific gravity evaluates the concentration of dissolved solids in the urine. Certain physiological conditions (e.g., uncontrolled diabetes) can result in unusually high specific gravity values. In sample validity testing for workplace urine specimens, the creatinine and specific gravity test results are reviewed together to conclude whether a specimen is dilute or replacement.

Valid urine specimens, as defined by the HHS Mandatory Guidelines, have a measured pH ≥4.5 and < 9.0, somewhat larger than the clinical range of 5.0 and 6.0 for healthy individuals, are expected to have a measured oxidant activity of less than that equivalent to 200.00 mcg/rnL of nitrite or 50.0 mcg/rnL of chromium VI, and have a measured creative of ≥20 mg/dL and a specific gravity (SpGr) ≥1.0030 and <1.0200 if they were measured.

Analytical Tests

A lot of commonly used adulterants in early days of drug testing were commercial cleaning products, which had unique and often very strong identifying characteristics such as smell. They often also altered the look of a sample so that it was easy to identify samples that had been adulterated. Adulterants that had an impact on the analytical test, particularly the immunoassay test, were also easy to make out by analytical results from the drug testing itself. Typically, the results would be contradictory with normal, negative, or positive results for all analytes. These specimens clearly stood out on review of the data.

In some cases, drug-testing laboratories do not have definitive specimen validity test results to support reporting a specimen as adulterated, but may suspect that a urine specimen has been adulterated based on its abnormal physical appearance or odor (i.e., precipitation, dark color, strong offensive odor), or on abnormal or unexpected results during initial and/or confirmatory testing for drugs i.e., using various immunoassays for initial tests and gas chromatography-mass spectrometry (GC-MS) for confirmatory tests. There are also cases in which a specimens specimen validity test results are outside the acceptable range, but are not clearly indicative of substitution or adulteration. The HHS Mandatory Guidelines include criteria for laboratories to account such specimens as invalid See Figure 5-1 and Appendix at the end of the chapter.

Drug-testing laboratories use various analytical techniques as the preliminary and confirmatory specimen validity tests. Examples include, but are not ignited to, calorimetry, refractometry For urine specific gravity), potentiometry (pH meter for pH, ion-selective electrode for adulterants), atomic absorption spectrophotometry (AAS) electrophoresis, Inductively coupled plasma-mass spectrometry (ICP-MS), ion chromatography (IC), high-performance liquid chromatography (HPLC), multi-wavelength spectrometry (MWS), and GC-MS.

Researchers and drug-testing laboratories have used apprehensive workplace drug-testing specimens, as well as samples spiked with known adulterants, in studies to recognize the effects of adulterants and to develop procedures and methods to combat their use. There are analytical tests that identify adulterant compounds in urine specimens. Drug-testing laboratories have implemented such tests or have revised their drug test methods to surmount the effects of adulterants.

As specific adulterants began to be more commonly used to thwart drug-testing procedures, laboratories began to identify the adulteration agent and develop testing procedures to detect its presence. In response, manufacturers of the commercial adulterant and substitution products have developed new products and/or altered their product. For example, some commercial adulterant products were found to contain nitrite (Klear™). Several investigators examined the adulterant and its effects as well as developing a test to identify its presence. In this case, it was not simply a matter of isolating and identifying the presence of the adulterant because nitrite is a compound routinely found in clinical samples. One study documented the presence and concentration of nitrite in urine samples not the result of exogenous addition of nitrite as an adulterant. The authors concluded it was possible to establish a scientifically valid, forensically defensible cutoff for nitrite to distinguish non-metabolic nitrite versus naturally occulting nitrite. Other testing included methods for the identification and quantification of nitrite in the samples to allow distinction above the cutoff for nitrite. Nitrite affected the drugs and assays to varying degrees, with several being significantly impacted by the adulterant.

Other investigators described methods to reverse the effect of nitrite adulteration. Drug-testing laboratories implemented procedures to identify this adulterant, and HHS issued guidance defining specimens with a nitrite concentration greater than or equal to 500 mcg/mL as being adulterated.

After the extensive efforts to identify the adulterant, characterize naturally occurring versus exogenously added nitrite and rule changing with all of the administrative effort and time to thwart this adulterant, some adulterant my altered their products to avoid detection of the adulterant compound while maintaining the deleterious effect on the drug test. These alterations included reducing the nitrite concentration below the HHS established cutoff lowering the phi, adding another oxidizing compound (e.g., chromate) to the product, and replacing nitrite with another oxidizing compound (e.g., hydrofluoric acid, per-iodate, and other halogens). This inevitable modification of products leads to a cycle of creation of an adulterant, followed by characterization and detection, followed by modification of the product, followed again by characterization and detection, and so on. This puts the program into a catch-up situation as it is far faster and easier for the adulterant manufacturer than the federal program. Add to this the administrative burden required for changes to the program and the tendency to assay for a process or general effect rather than a specific adulterant has been adopted by most labs. For example, rather than developing specific analytical tests for an adulterant, the test is designed to identify an adulterant that acts through the process of oxidation (a general oxidant test), making the testing and identification of many of the new or modified adulterants possible without a long identification and characterization process.

Urine substitution products also serve as examples of product evolution over time. Early substitution attempts involved the simple substitution of a drug-free liquid (e.g., water, another person’s urines for the donor’s specimen). Commercial substitution products followed, consisting of drug-free human urine, synthetic urine, or fortified aqueous solutions formulated to appear as human urine. These were sold as liquids or in the form of freeze-dried powders. To bypass specimen temperature checks performed by collectors, manufacturers added heating mechanisms to storage reservoirs as well as heat-sensitive tape to monitor the effectiveness of the heating mechanisms. These devices bring the substitution product within the acceptable temperature range for a recently voided human urine specimen (i.e., 90 – 100 °F). Various storage and delivery systems for the substitution products have been developed to avoid detection during collection. Some products today include prosthetic devices, so a donor can attempt to substitute their specimen even during an observed collection.

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