The Use of Z-Drugs to Facilitate Sexual Assault.

Zolpidem, zopiclone, and zaleplon are commonly referred to as the "Z-drugs." The Z-drugs are nonbenzodiazepine hypnotics indicated for the short-term treatment of insomnia. Since becoming widely prescribed as sleep aids in the United States, they are increasingly being detected in a variety of forensic specimens. We present a comprehensive overview of the basic chemistry, pharmacodynamics, and pharmacokinetics of zolpidem, zopiclone, and zaleplon, including their interaction with other prescription drugs and ethanol, findings in drug-facilitated sexual assault (DFSA) casework, and methods of analysis.

Deposition of 7-aminoflunitrazepam and flunitrazepam in hair after a single dose of Rohypnol.

In recent years, there has been a notable increase in the number of reports on drug-facilitated sexual assault. Benzodiazepines are the most common so-called "date-rape" drugs, with flunitrazepam (Rohypnol) being one of the most frequently mentioned. The aim of this study was to determine whether flunitrazepam and its major metabolite 7-aminoflunitrazepam could be detected in hair collected from ten healthy volunteers after receiving a single 2 mg dose of Rohypnol using solid phase extraction and NCI-GC-MS. Such data would be of great importance to law enforcement agencies trying to determine the best time interval for hair collection from a victim of drug-facilitated sexual assault in order to reveal drug use. Ten healthy volunteers (eight women and two men, 21 to 49 years old) participated in the study. The following hair samples were collected from each volunteer: one before flunitrazepam administration, and 1, 3, 5, 14, 21, and 28 days after. In five volunteers, 7-aminoflunitrazepam was detected 24 h after flunitrazepam administration and remained in hair throughout the entire 28-day study period (0.6-8.0 pg/mg). In two cases, 7-aminoflunitrazepam appeared in hair 21 days after drug intake (0.5-2.7 pg/mg), and in two subjects 14 days later (0.5-5.4 pg/mg). In one volunteer, 7-aminoflunitrazepam was detected on day 14 and 21 but concentrations were below the quantitation limit. Flunitrazepam was detected in some samples but all concentrations were below the quantitation limit (0.5-2.3 pg/mg).

Elimination of 7-aminoflunitrazepam and flunitrazepam in urine after a single dose of Rohypnol.

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.

Report of a fatal thiamylal intoxication.

A fatality due to the intravenous administration of thiamylal is reported. Quantitation of the drug was accomplished by high-performance liquid chromatography (HPLC) and confirmation was by gas chromatography/mass spectrometry (GC/MS). Postmortem tissue concentrations of thiamylal were as follow: 129 mg/L in blood, 366 mg/kg in liver, and 116 mg/kg in brain. Thiamylal was not detected in the urine, gastric contents, or bile. Analytical caveats involving the quantitation of thiamylal are also discussed.

Investigation of an acetaldehyde-hemoglobin adduct in alcoholics.

It has been proposed that an ethanol-related adduct is formed with hemoglobin in chronic alcoholics. This proposal is based on the observation that alcoholics were found to have an elevation of minor hemoglobins but normal amounts of glycosylated hemoglobin (HbA1c). Since acetaldehyde is believed to be the primary candidate involved in adduct formation, investigation was focused on this particular compound. This study describes the attempt to isolate and purify an acetaldehyde-hemoglobin adduct in alcoholics by cation-exchange chromatography and m-aminophenylboronic acid affinity chromatography for the purpose of characterization. Using acetaldehyde concentrations of 5 and 10 mM, an acetaldehyde adduct with hemoglobin was formed in vitro, isolated, and characterized. However, a similar adduct could not be isolated in vitro using a pharmacological concentration of 100 microM acetaldehyde nor could this adduct be isolated in human alcoholic subjects.

Detection of opiates in postmortem tissues by thin-layer immunoassay.

The use of thin-layer immunoassay (TIA) for the detection of opiates in postmortem brain, kidney, liver, and lung tissue has been developed. The method is simple to perform, requires no specialized equipment or radioactive reagents, and is sufficiently sensitive for the detection of opiates in postmortem tissues. Sample preparation consists of homogenization followed by ultradialysis to remove protein. The procedure was evaluated in a blind study of 83 postmortem tissue specimens and found to be reliable at tissue concentrations greater than or equal to 200 ng/g as determined by radioimmunoassay (RIA).