What is the primary metabolite of cocaine?

Primary Metabolite of Cocaine

The primary metabolite of cocaine is benzoylecgonine, which is formed through hepatic metabolism by plasma and liver cholinesterases and serves as the standard biomarker for cocaine detection in clinical and forensic settings. 1

Metabolic Pathway

• Cocaine undergoes detoxification primarily through plasma and liver cholinesterases, which form metabolic products that are excreted in the urine. 2
• Benzoylecgonine represents the main toxic metabolite after cocaine consumption and has a longer retention time in the body than cocaine itself. 3
• Additional metabolites include ecgonine methyl ester (the other major metabolite), norcocaine, and cocaethylene (when cocaine is co-consumed with alcohol). 4

Detection Characteristics

Standard Detection Window

• Benzoylecgonine has a urinary half-life of 6 to 8 hours and can be detected in urine for approximately 24 to 48 hours after cocaine use in typical cases. 1
• In a study of 18 patients who used cocaine intranasally, the mean time to the first negative urine specimen was 43.6 ± 17.1 hours (range 16 to 66 hours). 1

Extended Detection in Chronic Users

• Among individuals with long-term heavy cocaine use (who may ingest up to 10 g/day), benzoylecgonine has been detected up to 22 days after last ingestion. 1, 2

Clinical Testing Methodology

Standard Screening Approach

• Qualitative immunoassay detection of benzoylecgonine in urine is the most commonly used laboratory method, with cocaine use reported as positive when benzoylecgonine levels exceed the standard cut-off value of 300 ng/mL. 1
• Cocaine can also be detected in blood and hair, though urine testing remains the primary method. 1

Critical Testing Pitfall

• Testing for benzoylecgonine alone may result in false-negative determinations when cocaine is recently administered or metabolism is impaired—approximately 3% of cocaine-positive specimens contain parent cocaine without detectable benzoylecgonine. 5
• Of specimens testing positive for cocaine markers, 26% were positive for parent cocaine and 97% were positive for benzoylecgonine, with 3% showing cocaine only without benzoylecgonine. 5
• Of cocaine-only positive specimens tested by both LC-MS/MS and immunoassay, 81% were negative by immunoassay, demonstrating the limitation of screening with benzoylecgonine-specific immunoassays alone. 5

Confirmation Testing

• Gas chromatography/mass spectrometry (GC/MS) with stable isotope dilution using deuterium-labeled internal standards is required for forensic confirmation of benzoylecgonine presence. 6
• Both DRI® and Lin-Zhi International enzyme immunoassays demonstrate 98% overall agreement with GC/MS results, with sensitivity of 0.968 and 0.958 respectively. 7

Clinical Implications

• Quantitative methods for benzoylecgonine measurement are more expensive and potentially misleading due to individual variability in cocaine metabolism and excretion. 1
• The toxicity of benzoylecgonine to humans is as significant as cocaine itself, making its detection clinically relevant beyond simply confirming cocaine use. 3
• For optimal detection in clinical and forensic settings, testing should include both parent cocaine and benzoylecgonine to avoid false-negative results, particularly in cases of recent use or impaired metabolism. 5