title: Norcocaine in human hair as a biomarker of heavy cocaine use in a high risk population.
abstract: In hair analysis, cocaine (COC) and its metabolites have been studied relatively extensively with a consistent focus of distinguishing active drug use and excluding external contamination. Although quantitative cut-offs using major metabolite, benzolecgonine (BE), in hair have been proposed to distinguish likely active use from passive exposure, exogenously formed BE may result in false positive tests. Hence, the presence of less commonly detected COC metabolite, norcocaine (NCOC), may be useful in increasing certainty of illicit COC use and evaluating likelihood of environmental contamination. The objective of the present study was to observe the pattern of NCOC detection in a clinical population of suspected users and evaluate the possible role of NCOC in distinguishing systemic exposure from external contamination to COC and assessing intensity of cocaine use. Hair samples collected between January 2011 and May 2013 from the Motherisk Laboratory were analyzed by GC-MS for the presence of COC, BE, and NCOC. NCOC positivity rates (%) for various COC concentration ranges as well as sensitivity, specificity, positive predictive value, and negative predictive values of NCOC as a biomarker of different COC use profiles was calculated. The rate of NCOC positivity (%) within COC concentration ranges (ng/mg) 0.13-0.4 (above LOD, below LOQ), 0.4-3, 3-6, 6-10, 10-14, >14 were 0.26, 4.15, 29.63, 55.85, 80.37, and 94.02, respectively; p<0.0001 for all positivity comparisons between ranges. These results were used to determine a COC cut-off concentration for differing levels of COC use. The presence of NCOC above the LOD of 0.13 ng/mg predicted COC concentrations exceeding 14.00 ng/mg, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 94.0%, 87.9%, 41.5%, and 99.4%, respectively. The presence NCOC above the LOD of 0.13 ng/mg predicted COC concentrations exceeding the 75th percentile, with sensitivity, specificity, PPV, and NPV of 76.6%, 94.7%, 74.7%, and 95.2%, respectively. Despite an inability to definitively rule out external contamination, the presence of NCOC in hair is strongly associated with elevated COC levels and performs as a highly specific surrogate marker for frequent/intensive cocaine use and highly sensitive marker for intensive/daily use of cocaine.
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address: shirley.poon@sickkids.ca.
authors.forename: S
authors.initials: S
authors.lastname: Poon
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: joey.gareri@sickkids.ca.
authors.forename: J
authors.initials: J
authors.lastname: Gareri
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Walasek
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Western Ontario, Toronto, ON, Canada. Electronic address: gideon.koren@sickkids.ca.
authors.forename: G
authors.initials: G
authors.lastname: Koren
mesh_terms: D015415:Biomarkers / Q000032:analysis; D003042:Cocaine / Q000031:analogs & derivatives* / Q000032:analysis; D019970:Cocaine-Related Disorders / Q000175:diagnosis*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D009294:Narcotics / Q000032:analysis; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D009294:Narcotics; C008671:norcocaine; D003042:Cocaine
keywords: Benzolecgonine; Biomarker; Cocaine; Drugs of abuse; Hair; Norcocaine