Differentiating intentional ketamine use from unintentional exposure as an adulterant using oral fluid testing

Recreational ketamine use and related adverse outcomes have been increasing; however, correct diagnostic classification of quantitative oral fluid test results remains challenging, considering the potential for unintentional exposure to ketamine as an adulterant in other drugs. We surveyed and collected oral fluid from 1819 adults entering nightclubs and compared detection results with past 24-h self-reported ketamine use. Other drug use (based on detection and on self-reported past 24-h use) was considered a risk factor for unintentional ketamine exposure as an adulterant. Oral fluid specimens were analyzed via liquid chromatography quadrupole time-of-flight mass spectrometry. 10.8% of participants reported past 24-h ketamine use, 23.7% tested positive for ketamine (≥ 1 ng/mL), and 10.9% tested positive for norketamine (≥ 1 ng/mL). 46.0% tested positive for drugs other than ketamine, primarily cocaine. Among those testing positive for ketamine (n = 431), 41.5% reported past 24-h use. Among these cases, the optimal ketamine concentration cut-point for predicting self-report was ≥ 18 ng/mL. In analyses using the full sample (n = 1819) and a subsample with data on past 48-h use (n = 795), optimal cut-points were ≥ 2 ng/mL and ≥ 5 ng/mL, respectively. However, norketamine detection was the strongest predictor of self-reported use across the full sample and subsamples examined. Using self-report as the comparison, norketamine detection most accurately classified reported use; however, relying solely on higher concentration thresholds of ketamine or norketamine detection alone may lead to underdetection in some cases. Findings indicate the importance of carefully selected biological markers and thresholds when interpreting oral fluid results in settings where adulterant exposure is common.