7-Aminoclonazepam is superior to clonazepam for detection of clonazepam use in oral fluid by LC–MS/MS

• Published in: Clinica chimica acta Vol. 455; pp. 128 - 133
• Main Authors: Melanson, Stacy E.F., Griggs, David, Bixho, Ida, Khaliq, Tahira, Flood, James G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2016
• Subjects: 7-Aminoclonazepam; Addiction management; Calibration; Chromatography, Liquid - methods; Clonazepam; Clonazepam - administration & dosage; Clonazepam - analogs & derivatives; Clonazepam - metabolism; Compliance; Humans; Oral fluid; Reproducibility of Results; Saliva - metabolism; Tandem Mass Spectrometry - methods; Compliance; MS; 7-Aminoclonazepam; OXAZ; Clonazepam; LC–MS/MS; PRN; MDMA; CLON; OF; BZ; Addiction management; 7AC; Oral fluid
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2016.01.027

Clonazepam (CLON) is not only frequently prescribed in addiction management but is also commonly abused. Therefore many addiction clinics perform oral fluid (OF) testing, which unlike urine is not subject to adulteration, to monitor CLON compliance. However, CLON and other benzodiazepines can be challenging to detect in OF due to their weakly acidic nature and their presence in low concentrations. We determined the optimal technical and clinical approach for the detection of CLON use using OF. We measured CLON and its primary metabolite 7-aminoclonazepam (7AC) by liquid chromatography–tandem mass spectrometry in OF specimens over a 2month period. The samples were collected using the Orasure Intercept OF sample collection device. One hundred samples were presumptive-positive for 7AC and/or CLON. 91 (91.0%) confirmed positive for 7AC (median, range: 4.2, 0.5–316.7ng/ml) using the ion ratio test, while only 44 of the 100 (44.0%) samples confirmed positive for CLON (median, range: 3.7, 0.5–217.2ng/ml) using the ion ratio test. In OF the levels of 7AC were approximately 2.4-fold higher than CLON. The use of 7AC as an analyte for the detection of both CLON compliance and undisclosed use is also recommended. 7AC should be the analyte measured in OF for the detection of CLON use. •OF is becoming increasingly popular as a tool to monitor compliance in the addiction setting.•CLON can be challenging to measure in OF due to its presence in low concentrations.•We demonstrate that 7AC is superior to CLON for monitoring CLON use.•Clinically, 7AC is superior to CLON for detection of both CLON compliance and undisclosed use.•Laboratories performing OF testing should validate and implement 7AC in OF for the assessment of CLON use.