Our cellular regulatory processes, including plants, break down or metabolize food and other substances into different small molecules or metabolites. A metabolite is a byproduct of cellular metabolism in the body. The process of metabolizing drugs in the body occurs in the same manner. For instance , THC in Marijuana is metabolized into tetrahydrocannabinol carboxylic acid (THC-COOH), the primary metabolite of Marijuana. Cocaine is metabolized into benzoylecgonine as the major metabolite. Similarly, the presence of 6-MAM (monoacetylmorphine) or morphine metabolites is indicative of Heroin (diacetylmorphine) or other opiates use. The presence of a drug metabolite is a reliable indicator of the parent drug intake in the body.
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Read on to know more about drugs and their metabolites, and the different drug tests for detecting them.
Drug metabolites are broken down in the liver by the cytochrome P-450 enzymes before being expelled into the intestine through the biliary tract. They are then reabsorbed by the kidneys in the form of urine or passed with feces. The ability of the cytochrome P-450 enzymes to metabolize a drug in the body ensures reduced side effects that the use of a specific drug may bring about.
Instead of detecting a parent drug, many standard drug testing methods look for the presence of metabolites. Many metabolites remain in the body long after the parent drug has been expelled. This ensures greater true positive test rates by identifying and detecting the metabolite rather than the parent drug quickly expelled by the body. It is no wonder why most drug kits in the market don’t detect the drugs mentioned on the kit. However, that does not mean they are fraudulent since these drug testing kits are essentially designed to detect the presence of metabolites of the parent drug named on the kit.
Metabolites and drug tests
Here is a list of some of the common parent drugs and their metabolites for which standard drug tests are being performed.
Cocaine
Cocaine has a half-life of roughly six hours in the human body. This essentially Cocaine alkaloid will be present in the urine for a day after last use. However, benzoylegonine, cocaine's primary metabolite with a half-life of 12 hours and lasts in the body for up to 4 days. Most drug tests for cocaine are carried out to detect the presence of benzoylegonine along with cocaine.
Marijuana
The primary metabolite in Marijuana is 11-Nor-9-carboxy-9-tetrahydrocannabinola(THC -COOH). The parent drug, delta-9- tetrahydrocannabinol, has a half-life of less than 30 minutes and is not detectable in urine. THC-COOH, on the other hand, has a long half-life and is detectable in the plasma for as long as one week. It takes an hour or so for the THC-COOH metabolite to appear in the urine, but sometimes it can take as long as 4 hours. Urine drug tests typically detect THC-COOH metabolite's presence as it lasts in the urine for a more extended period.
Nicotine
Cotinine is the primary metabolite of nicotine in tobacco. Cotinine has an average half-life of 19 hours in the human body, much longer than the parent drug nicotine. Urine drug tests for nicotine in tobacco essentially look for the presence of cotinine for indicating the use of tobacco.
Opioids
At least 140 people die from overdose in the U.S. Two-thirds of these deaths arise from opioids. Opioids are generally prescribed for pain management. Its affordability and ease of availability have made it a popular drug for illicit use. Drug tests for detecting opioids and their metabolites are performed to ensure safety and efficacy in therapy, examining adherence to prescribed levels of opioid ingestion, monitoring someone with opioid addiction, and detecting and measuring opioid overdose. Urine is the most frequently tested sample for opioids. A urine test can help detect natural opioids like morphine and codeine alkaloids found in opium and semisynthetic opioids such as oxycodone and hydrocodone. Some synthetic opioids like Heroin (diacetylmorphine) and naloxone are also detectable through urine screening. Urine tests detect the presence of opioids similar to morphine. Most synthetic opioids such as fentanyl, meperidine, and methadone are not detected. Alternatively, serum, hair, saliva, and even sweat samples are collected to detect these classes of opioids and their metabolites.
The table below lists some of the common opioids and their metabolites:
|
Parent drug |
Primary metabolite |
|
Heroine |
6 MAM, Morphine |
|
Morphine |
3-Morphine-Glucuronide, 6-Morphine-Glucuronide |
|
Codeine |
Morphine |
|
Hydrocodone |
Hydromorphone, Norhydrocodone |
|
Oxycodone |
Oxymorphone, Noroxymorphone |
|
Naloxone |
Noroxyorphone |
|
Fentanyl |
Nrfentanyl |
|
Meperidine |
Normeperidine |
|
Methadone |
EDDP(2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) |
Alcohol
Alcohol or ethanol is absorbed into the blood from the stomach and intestines. It is then metabolized by enzymes in the liver. In the liver, alcohol is metabolized by different processes or pathways. The most common pathway involves two enzymes- alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) that help break down the alcohol molecule and eventually eliminate it from the body. ADH transforms ethanol into a compound called acetaldehyde, a known carcinogen. Acetaldehyde is short-lived and further metabolized into a less toxic compound called acetate by the ALDH enzyme. Acetate in the body is further broken down to carbon dioxide and water in tissues other than the liver.
The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down ethanol to acetaldehyde. CYP2E1 is triggered mainly after a heavy drinking bout or binge drinking and catalase on the other hand is responsible for metabolizing a small fraction of ethanol. Most of the alcohol is metabolized in the liver. However, small amounts of alcohol are removed by interacting with fatty acids to form compounds called fatty acid ethyl ester (FAEEs), which have been shown to cause damage to the liver and pancreas. A small fraction of alcohol that is not metabolized is eliminated through the breath and urine.
Alcohol can be detected in urine drug screens, but a breath test for alcohol detection remains the most preferred testing method. These tests measure the blood alcohol concentration (BAC), which refers to the amount of alcohol in the blood in relation to the amount of water in the blood. A ethyl glucuronide (EtG) test is also used to detect ethyl glucuronide- a metabolite of ethanol in the urine. EtG tests are mainly used to detect alcohol abstinence in cases that prohibit the use of alcohol.
The takeaway
The absence of a standard drug testing method adds to the problem of selecting the proper test, collecting samples, and interpreting results. The problem is further exacerbated by the fact that most drugs have a short life duration in the body. The time for which a particular drug and its metabolite can be detected in the body varies from one drug to another, i.e., the drug's pharmacokinetic properties, the patient's metabolism, the dosage of a drug, and the quality and choice of a specimen. Many metabolites remain in the body long after the parent drug has been expelled. The detection of metabolites, in this sense, plays an essential role in determining the result of a drug test. The detection of metabolites in the body allows for a reliable prediction and accurate finding of a drug test result.
