William E. Schreiber - An Introduction to Testing for Drugs of Abuse

Drug Excretion

www.msdmanuals.com/professional/clinical‐pharmacology/pharmacokinetics/drug‐excretion

Pharmacokinetics 1 – Introduction

www.youtube.com/watch?v=8‐Qtd6RhfVA

Pharmacokinetics 2 – Absorption

www.youtube.com/watch?v=pWW‐aq7iSa0

Pharmacokinetics 3 – Distribution

www.youtube.com/watch?v=6erefsWCVxg

Pharmacokinetics 4 – Metabolism

www.youtube.com/watch?v=ztsBn8gsfHw

Pharmacokinetics 5 – Excretion

www.youtube.com/watch?v=VZRVt9r4oSM

Testing for drugs and toxins can be performed on a variety of specimens. Choosing the most appropriate one depends on the purpose of the analysis.

Blood is the specimen of choice for assessing the amount of active drug in a patient. This information is required in a number of situations, such as:

monitoring the concentration of a prescribed drug to ensure therapeutic levels are present (eg, carbamazepine in a patient with epilepsy)

measuring the amount of a potentially toxic drug to guide therapy and assess prognosis (eg, acetaminophen in a patient who took an overdose)

identifying a cause for altered mental status (eg, ethanol in a comatose patient).

In most cases, drugs are measured in serum. Whole blood is required for certain analyses, because the drug or toxin of interest accumulates within red blood cells.

Collecting blood is an invasive procedure – inserting a needle through skin into a vein – and it causes anxiety and discomfort to some patients. Experienced phlebotomists can draw blood with little or no associated pain, and they ensure that the sample is from the person on whom it was ordered.

Urine is the best sample for determining whether someone has taken a drug within the recent past. It is an aqueous fluid that contains both drugs and their metabolites in a concentrated form. The window of detection varies from hours to a week or longer, depending on the specific drug and how much was taken.

Urine drug testing is ordered for a number of reasons.

Confirm or rule out a suspected acute drug intoxication (eg, patient in the emergency room with symptoms of a drug ingestion).

Discover use of illegal or prohibited drugs (eg, employment drug screening program).

Monitor patients with a history of drug abuse (eg, drug rehabilitation program).

Ensure compliance with drug prescriptions that might be diverted (eg, opioid screening in pain management clinics).

Urine is easy to collect and does not require special handling. Point‐of‐care screening tests can be performed directly on the sample with no additional preparation. Most compounds of interest are excreted in urine, so recent consumption of a drug is likely to be detected in this sample.

The main drawback of a urine sample is that it can be tampered with by the owner before analysis. The issue of specimen validity testing (SVT) is discussed later in this chapter.

Oral fluid consists mainly of the mixed saliva that comes from three major and several minor salivary glands. Small amounts of cellular debris, bacteria, and the residue of ingested substances are also present. It is more than 99% water and contains electrolytes, proteins, enzymes, and other biomolecules.

Drugs appear in oral fluid by passive diffusion from blood. The rate of transfer is related to the chemical properties of a drug and the degree of binding to plasma proteins (only free drug molecules can diffuse across capillary walls).

The window of detection is several hours to several days following drug use, depending on the specific drug and the amount and frequency of consumption. One advantage of oral fluid over other samples is that recently ingested (e.g., ethanol) or smoked (e.g., tetrahydrocannabinol) drugs may leave a residue that is present in high concentration.

Oral fluid is a noninvasive specimen and is easy to obtain with commercial collection devices. The collection process can be witnessed to prevent sample adulteration or substitution. It is especially useful in roadside testing for drugs that impair a person's ability to drive.

Drugs in blood diffuse into the hair follicle, where the hair shaft grows. As the keratin matrix of hair is formed, drugs are incorporated and remain there, moving outward as the length of the hair shaft increases. A human hair is therefore a biological record of drug exposure.

The unique advantage of hair testing is the extended time period over which drugs can be detected. Hair samples can test positive as early as 1 week following drug use, and the window of detection is months or even years, depending on hair length.

Hair is usually collected from the crown of the head. The average growth rate for hair at this site is about 0.5 in (1.3 cm) per month. Sample collection is fairly simple – multiple strands of hair are cut at scalp level and sent to a testing facility for analysis. Collection can be witnessed or performed by trained personnel to prevent substitution or adulteration of the hair sample.

The laboratory may test a defined length of hair, which corresponds to an approximate period of time (i.e., hair trimmed to 1.5 in will detect drugs taken within the past 3 months). It is also possible to cut hair into short segments, which are analyzed separately. By comparing the test results on adjoining hair segments, an approximate timeline of drug exposure can be determined.

Analysis of drugs in hair is technically more demanding than other specimens. Hair samples must be washed to eliminate any surface contamination, and drugs must then be extracted from the hair shaft into a liquid medium that can be analyzed. This is a specialized procedure that is not available in most routine toxicology laboratories.

Other sample types are informative in specific situations.

Meconium is the greenish‐black stool passed by a newborn following delivery. Analysis of this material can detect drug exposure in utero (i.e., drug use by the mother during pregnancy).

Sweat can be collected with an absorbent skin patch for up to 1 week. Analysis of the accumulated sweat will indicate whether drugs have been consumed during that time period.

Many people are required to undergo drug testing as a condition of employment or to remain in drug rehabilitation programs. Testing is most often performed on urine because it is easy to obtain, and both drugs and their metabolites are present in concentrated form.

Collection of urine samples is not usually witnessed. The person providing the sample may try to get a “clean” test result by tampering with the specimen before submitting it. Specimen tampering can be divided into three categories.

Adulteration – a substance is added to the specimen that masks the presence of drugs and their metabolites. The substance may interfere with the analytical method or it may react with the drug(s) of interest to produce compounds that are not detected. Bleach, vinegar, ammonia, and other household products have been used for this purpose. More sophisticated operators use additives that interfere with drug tests but are hard to detect. These adulterants include nitrite, chromate, peroxide, halogens (all of which are oxidizing agents), and glutaraldehyde. Commercial products with amusing names like Whizzies, UrineLuck, and Stealth are available on the internet and in drug paraphernalia shops.

Substitution – the patient substitutes another sample for their own urine. It could be a friend's urine, a synthetic urine product, a yellow‐colored fluid such as apple juice, or tap water. Since the sample does not come from the patient, it will test negative (unless they pick the wrong person to provide the substitute sample!).