Defining Definitive Drug Testing Codes
Break down the code descriptors for proper drug test reporting.
Definitive drug testing code descriptors may contain terms not familiar outside the laboratory. To better understand these codes (G0480-G0483), let’s look at a typical descriptor and discuss relevant concepts.
HCPCS Level II code G0480 is a perfect example:
G0480 Drug test(s), definitive, utilizing drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to GC/MS (any type, single or tandem) and LC/MS (any type, single or tandem and excluding immunoassays (eg, IA, EIA, ELISA, EMIT, FPIA) and enzymatic methods (eg. Alcohol dehydrogenase)); qualitative or quantitative, all sources, includes specimen validity testing per day, 1-7 drug class(es), including metabolite(s) if performed
How Isomers Affect Drug Testing
The terms “structural isomers” and “stereoisomers” are probably your first roadblocks. CPT® describes these as “compounds that have the same molecular formula but differ in structural formula.” For example, butane has a molecular formula of C4H10 (four carbon atoms and 10 hydrogen atoms). Isobutane has the same chemical formula but, whereas butane has four carbon atoms bonded in a continuous chain, isobutane has a branched structure, as shown in Figure 1.
Figure 1: This is a structural isomer.
Source: Encyclopedia Britannica: www.britannica.com/science/isomerism
The structure of pharmaceuticals is more complex, but the concept is the same.
Stereoisomers have the same molecular formula, but differ in how they are structured in space. An example is cis-2-butene and trans-2-butene. Both have a molecular formula of C4H8, but differ in structural orientation, as shown in Figure 2:
Figure 2: These are stereoisomers.
McGraw-Hill Dictionary of Scientific & Technical Terms, 6E, Copyright© 2003 by The McGraw-Hill Companies, Inc.
The prefix cis is Latin for “on this side,” and trans means “across.” In this orientation, the CH3 groups are on the same side in the “cis” orientation and across from each other in the “trans” orientation.
Definitive test methods can distinguish between structural isomers (isobutane and butane), but not always stereoisomers (cis and trans orientation).
Understand Chromatography and Spectrometry
The next terminology that may hang you up is gas chromatography/mass spectrometry (GC/MS), which is an analytical method that combines the differentiation ability of gas chromatography with the identification ability of mass spectrometry.
Gas chromatography vaporizes a solution containing the substance (drug). The vaporized sample is carried by the gas (mobile phase) through a microscopic layer of liquid or polymer (stationary phase) inside a piece of glass or metal tube, referred to as a column. Different chemicals will flow through the column at different rates, allowing for separation of materials carried by the gas. As the chemicals are separated, they enter a mass spectrometer for identification, as shown in Figure 3.
Figure 3: A mass spectrometer identifies chemicals.
The mass spectrometer is used to determine the chemical constituents or analytes in a chemical sample. The results of a mass spectrometer analysis are generally in the form of a graph showing the distribution of components. Software is used to match the components to known standards to identify the sample. Figure 4 shows the mass spectrometer results for heroin.
Figure 4: A graph shows the distribution of components.
Electron-impact mass spectrum of heroin, Aibolita: http://aibolita.com/addiction-treatment/45732-electron-impact-mass-spectrometry.html
Mass spectrometers use the difference in mass-to-charge ratio of ionized atoms or molecules to separate them, allowing for quantitation and structural information by identifying distinctive fragments. The sample enters the spectrometer, where it is ionized into a gas. It then enters the mass analyzer, where its ions are sorted and passed onto the ion transducer that detects the ions. Information gathered is sent to a signal processor, where software analyzes the results, as shown in Figure 5.
Figure 5: Software analyzes the results.
Make Sense of Liquid
Chromatography/Mass Spectrometry (LC/MS)
In simple terms, the difference between gas and liquid chromatography is the carrier method — either an inert gas for gas chromatography or an inert liquid for liquid chromatography.
Metabolites — our final buzz word — are the breakdown products of a compound. For example, heroin is metabolized as shown in Figure 6.
Figure 6: This is how heroin is metabolized.
Source: United Nations Office on Drugs and Crime, Metabolic pathway of heroin.
When monitoring or diagnosing patients with a positive screen for morphine, clinicians must consider that heroin and codeine, among other compounds, metabolize into morphine.
Put It All Together
Definitive drug testing is used to test a sample for identifying compounds contained within. Gas or liquid chromatography is used to separate the constituent compounds, and mass spectrometry is used to definitively identify them. These methods can differentiate between isomers or shapes to distinguish between biologically active and inactive forms.
Drug testing is useful for monitoring patient treatment compliance with prescribed medications that have addictive properties (e.g., opioid pain medications, sedatives, and attention-deficit/hyperactivity disorder medication). Test results determine whether patients have recently taken their prescribed medication and if non-prescribed or illicit drugs have been used. A provider may order a urine drug screen (HCPCS Level II code G0431 Drug screen, qualitative; multiple drug classes by high complexity test method (eg, immunoassay, enzyme assay), per patient encounter), for example, to obtain a baseline before initiating pain management treatment. If the screen comes up positive for opioids and barbiturates after the patient has denied medication use, the provider may order definitive drug testing (HCPCS Level II code G0480) to determine exactly what medications were in the patient’s urine.