ABSTRACT
Clonazepam (CLO) is an anticonvulsant benzodiazepine approved by the Food and Drug Administration for use in the treatment of seizures. It produces pharmacological effects (depression, amnesia) similar to other compounds from the same therapeutic class, and in combination with alcohol, its CNS-depressant action can be significantly potentiated. As with some other benzodiazepines, CLO is a drug possibly used in "date-rape" situations. A method using solid-phase extraction followed by a highly sensitive negative chemical ionization gas chromatography-mass spectrometry for the simultaneous quantitation of CLO and its major metabolite 7-aminoclonazepam (7-ACLO) in hair was developed and validated. The method has potential application to alleged drug-facilitated rape cases. To determine the feasibility of detecting 7-ACLO and CLO in hair, specimens were collected from 10 psychiatric patients treated with CLO, divided into 2-cm segments, and analyzed. Standard curves for 7-ACLO (1-1000 pg/mg) and CLO (10-400 pg/mg) had correlation coefficients of 0.998. All precision and accuracy values were within acceptable limits. 7-ACLO was present in measurable quantities (1.37-1267 pg/mg) in 9 out of 10 patient samples. CLO concentrations in hair were much lower (10.7-180 pg/mg). In 4 out of 10 cases, CLO was not detected in hair. Two patients who had never been treated with CLO before received a single 2-mg dose of the drug. Approximately three weeks later, hair samples were collected, and measurable quantities of 7-ACLO (4.8 pg/mg) were detected in the first segment (proximal) of one of those samples, and traces of the drug were present in the other sample. We concluded that the 7-ACLO is being deposited in hair in much higher quantities than the parent drug and remains there for extended periods of time. Our study also indicates that it is possible to detect 7-ACLO after a single dose of CLO as in the typical date-rape scenarios.
Subject(s)
Anticonvulsants/analysis , Anticonvulsants/metabolism , Clonazepam/analysis , Clonazepam/metabolism , Hair/chemistry , Adult , Aged , Clonazepam/analogs & derivatives , Female , Gas Chromatography-Mass Spectrometry , Humans , Male , Middle Aged , Rape/diagnosis , Rape/legislation & jurisprudence , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The hypnotic benzodiazepine flunitrazepam (Rohypnol) has been identified as the drug of choice for the purposes of "drugging" unsuspecting victims and raping them while they are under the influence of this substance. The objective of this paper was to study elimination of flunitrazepam and 7-aminoflunitrazepam in urine collected from ten healthy volunteers who received a single 2 mg oral dose of Rohypnol, to determine how long after drug administration 7-aminoflunitrazepam can be detected. A highly sensitive NCI-GC-MS method for the simultaneous quantitation of flunitrazepam (LOQ 100 pg/mL) and 7-aminoflunitrazepam (LOQ 10 pg/mL) in urine was developed. All samples were screened for benzodiazepines using optimized micro-plate enzyme immunoassay. The highest concentrations of 7-aminoflunitrazepam (70-518 ng/mL) and flunitrazepam (0.7-2.8 ng/mL) in urine were observed 6 h after drug administration in nine subjects and after 24 h in one subject. In six subjects 7-aminoflunitrazepam was detected up to 14 days after flunitrazepam administration, in one subject up to 21 days and in three subjects up to 28 days. In urine samples collected from six volunteers, flunitrazepam was detected three days after Rohypnol intake, in three subjects 24 h, and in one subject 5 days later. Benzodiazepine micro-plate enzyme immunoassay kit allowed the detection of flunitrazepam and metabolities 5 to 21 days after drug administration.
Subject(s)
Anti-Anxiety Agents/urine , Flunitrazepam/analogs & derivatives , Flunitrazepam/urine , Adult , Anti-Anxiety Agents/administration & dosage , Female , Flunitrazepam/administration & dosage , Forensic Medicine , Gas Chromatography-Mass Spectrometry , Humans , Immunoassay , Male , Middle Aged , Rape , Time FactorsABSTRACT
Calcium channel antagonists (CCAs) have many clinical applications, including their possible use in the treatment of bipolar disorder. Two justifications for this last application are some overlap in physiological activities of CCAs with those of lithium, and a possible association between bipolar disorder and calcium dysregulation. While the data from earlier studies support the use of verapamil in treating bipolar mania. more recent better-controlled trials have not. This paper reviews the available body of data regarding CCAs in the treatment of bipolar disorder, concluding there is presently limited support for their efficacy.
