**2. Urine drug testing**

Traditionally, UDT has been associated with forensic testing, often referred to as workplace testing, to detect illicit drug use in employees. Workplace UDT has traditionally focused on identifying use of abused drugs including amphetamines (methamphetamine), cocaine, marijuana, phencyclidine (PCP), and heroin (opiates) (Federal Register - Mandatory Guidelines and Proposed Revisions to Mandatory Guidelines for Federal Workplace Drug Testing Programs [Federal Register], 2004). This type of testing is oriented toward determining positive results; that is, identifying the presence of an illicit substance. The reasoning behind this focus is obvious; a positive result for a prohibited substance is a cause for a consequence such as job dismissal (Federal Register, 2004). Testing for these drugs usually follows scheduled guidelines established by the Substance Abuse and Mental Health Services Administration (SAMHSA) (Federal Register, 2004). Analytically, the testing involves qualitative immunoassay screening followed by confirmation by mass spectrometry. Testing for patients on chronic opioid therapy is a different paradigm as both positive and negative results are important. It also requires assays that are more sensitive and can determine both the parent drug and one or more of its metabolites.

#### **2.1 Immunoassays**

26 Toxicity and Drug Testing

attempt to minimize the side effects by taking less of the medication when side effects are particularly debilitating or unpleasant. "Chronic pain patients often adjust their dose of prescribed medication in response to changing levels of activity with no malicious or maladaptive intent. Although they may state that their pattern of use of medications is stable, this is often a statement made ''on average'' rather than a precise pattern of use. This is particularly evident with short-acting medications used in the treatment of breakthrough

UDT is used to give confidence to both the physician and the patient that the patient is following the medication regimen and is therefore getting the most benefit from their treatment. In addition, the side effects of these medications often result in their misuse, underuse, and/or mixing of medications that are not prescribed (Manchikanti et al., 2004). This can also result in the social problems of abuse, misuse, or diversion of these medications. These factors require of pain physicians that they be particularly attentive to their prescribing practices. Adding to the complexity of managing pain patients is the fact that these medications are controlled substances and cannot be purchased over the counter, and so have high street value (Katz et al., 2003; National Prescription Drug Threat Assesment, 2009). This in turn requires of the physician that he or she determine whether patients under their care are compliant with their medication regime, binging on their medications, or diverting them for financial gain (Manchikanti et al., 2005, 2006a, 2006b).

Further compounding the situation, alcohol use is of major concern to the physician because alcohol-drug interactions can cause morbidity (Harmful Interactions: Mixing Alcohol with Medicines, 2007). Although physicians prohibit patient alcohol use during treatment with opiates or benzodiazepines, verbal contracts are commonly broken and therefore alcohol use must be monitored with (UDT) to manage the high risk of alcohol-drug reactions and mortality (Chou et al., 2009; Trescot et al., 2006). In addition, for reasons involving inadequate pain control, sleep deprivation, and psychological pathology, this patient population commonly takes other medications not prescribed by treating physicians as well as illicit drugs (Manchikanti et al., 2005, 2006a, 2006b). To respond to these potential problems, physicians traditionally relied upon behavioral assessment and pill counts to aid them in making treatment decisions. UDT has augmented these tools by providing physicians with objective, scientifically measurable outcomes to help them make decisions (Gourlay et al., 2010; Hammett-Stabler & Webster, 2008; Nafziger & Bertino, 2009; Reisfield et al., 2007). A detailed protocol of how to appropriately prescribe these controlled substances for this population is discussed in the book *Universal Precautions*, by Gourlay and

Traditionally, UDT has been associated with forensic testing, often referred to as workplace testing, to detect illicit drug use in employees. Workplace UDT has traditionally focused on identifying use of abused drugs including amphetamines (methamphetamine), cocaine, marijuana, phencyclidine (PCP), and heroin (opiates) (Federal Register - Mandatory Guidelines and Proposed Revisions to Mandatory Guidelines for Federal Workplace Drug Testing Programs [Federal Register], 2004). This type of testing is oriented toward determining positive results; that is, identifying the presence of an illicit substance. The

pain." (Gourlay & Heit, 2010b)

**1.3 Complications of pain treatment** 

Heit (Gourlay et al., 2005).

**2. Urine drug testing** 

Immunoassays are tests that are based on the ability of an antibody to bind with a drug (Feldkamp, 2010). Antibodies are made in such a way that they bind with a specific drug, such as morphine. In one approach, manufacturers of point of care (POC) devices embed test strips with antibodies and install them in devices designed to interact with urine specimens (Amedica Drug Screen Test Cup). A urine specimen with the drug in it (in this example, morphine) will displace the drug-indicator molecule on the test strip causing the morphine drug indicator line to disappear or change color. These test strips are then visually inspected by the person administering the test. The absence or presence of a line or the change in color, such as on a home pregnancy test, indicates whether the result is positive or negative. The immunoassay antibody binding reaction can be measured in other, more sophisticated ways than using test strips, such as reference laboratory analytical instruments (Olympus Au640 Product Information; Siemens V-Twin Analyzer Product Information; Thermo Fisher Mgc-240 Analyzer Product Information). However, the fundamental property of immunoassays is always the binding reaction of the antibody to the test drug (analyte).
