4.49: Drugs of Abuse in Urine

A 21 y/o Caucasian female has been enrolled in a court-ordered methadone clinic for the past 6 months, two months ago she gave birth to a healthy infant. At the time of delivery, she was drug-free. A routine sample of urine was obtained at her regular methadone clinic visit. The results are:

• OPIATES: POSITIVE
• METHADONE: POSITIVE
• BENZODIAZEPINES: NEGATIVE
• COCAINE: POSITIVE
• BARBITURATES: NEGATIVE
• ALCOHOL: NEGATIVE
• CREATININE: 230 MG/DL

Her physician calls the laboratory director, explaining that the patient is extremely upset, denying taking any drug except methadone. She is concerned that, on the basis of these results the judge assigned to her case will remove her infant from her care.

QUESTION

What steps should you take to investigate the problem and what would you tell the physician?

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At her next regular clinic visit she produces another urine.

• OPIATES: NEGATIVE
• METHADONE: POSITIVE
• BENZODIAZEPINES: NEGATIVE
• COCAINE: NEGATIVE
• BARBITURATES: NEGATIVE
• ALCOHOL: NEGATIVE
• CREATININE: <10 MG/DL

The laboratory director and the patient’s physician review the results and agree to send the sample for GC/MS confirmation.

QUESTION

Why was the sample sent for GC/MS confirmation?

Questions to Consider

1. What types of techniques are most frequently used to screen for drugs of abuse in urine (DAU)?
2. What type(s) of interferences are most likely to be encountered with DAU assays?
3. Does the patient’s physiological state have any impact on your response to the physician?
4. Are there ways that patients undergoing DAU screening might try to confound the laboratory results?

Answer

1. You first review the laboratory data to be sure that there were no obvious problems with the assay at the time of analysis. If the sample is still available in the laboratory, repeat the analysis. If the initial analysis appeared to be without problems and if the repeat analyses yielded similar results to the initial results, let the physician know that likelihood that all the positive results are incorrect is very small. Describe the assay to the physician, explaining the known interferences and cross-reactivities. Suggest the possibility of a mislabeled sample and suggest that the physician order a repeat analysis on a new sample as soon as possible.
2. Because of the low creatinine and the socio-medical nature of the case, the sample was sent for GC/MS analysis. The immeasurable creatinine suggests that the sample was not urine or is a doctored urine sample ‘spiked’ with methadone. GC/MS analysis finds only the parent drug of methadone present; methadone metabolites are NOT present, which strongly suggests that this was some sort of doctored sample.

Answers to Questions to Consider

1. The most common assays for the detection of drugs in urine are chromatographic (HPLC, GC, and GC/MS; see chapter 6, 7, and 8 respectively) and immunologic (see chapter 13). The greatest percentages of screening tests are performed by competitive binding immunoassays (see chapters 13 and 51).
2. For the all assay types the major problem is one of compounds that closely resemble the drug to be measured interfering in the assay. For chromatographic assays the interfering compounds have physical/solubility properties that closely resemble the drug and so closely- or co-chromatograph with the drug. For immunoassays, the interfering compounds cross-react with the antibody used in the assay. In all cases, the interference causes false positive results. Endogenous antibodies interfering in monoclonal-based assays, HAMAs, can also be a problem.
3. Yes. One of the major problems with people addicted to drugs is that they are in a state of denial, denial of their problem and denial of the steps needed to correct their addiction (see chapter 52). This often leads to addicts who are clearly on drugs to deny that they could possibly have a positive DAU test and complaining of inaccurate drug analysis. Of course there is always the possibility of a mislabeled sample.
4. Yes, the following is just a sampling of such attempts to force the laboratory to produce falsely negative results
   • Adding a compound that might destroy the assay, such as by inhibiting an enzyme
   • Obtaining (often purchasing) urine known to be negative
   • Diluting their urine with toilet water
   • Substituting a liquid that looks like urine but is not.