Recommendations for toxicological investigations of drug-facilitated sexual assaults.

The recent increase in reports of drug-facilitated sexual assaults has caused alarm in the general public and prompted forensic toxicologists from across North America to address the toxicological issues surrounding this matter. The authors have developed recommendations and guidelines to inform law enforcement, medical, and scientific personnel of the requirements for performing successful toxicological examinations in cases of drug-facilitated rape.

Hydrogen sulfide poisoning: clarification of some controversial issues.

BACKGROUND: Hydrogen sulfide is a toxic gas about which much has been written. We discuss here several issues we believe would benefit from further clarification. CONCLUSIONS: We conclude that: 1) Certain neurotoxic effects of exposure are probably due to a direct toxic effect on the brain, while others are almost certainly a result of hypoxia secondary to H2S-induced respiratory insufficiency; 2) pulmonary edema is a common consequence of poisoning and there is suggestive evidence of hyperactive airway responses in some individuals following brief H2S-induced unconsciousness (knockdown); 3) criteria for acceptable community levels are very different than those governing occupational standards; 4) urinary thiosulfate determinations can be useful for monitoring occupational exposure; and 5) determination of sulfide ion concentrations in blood or major organs can be useful in corroborating a diagnosis of fatal H2S toxicity, but there are many pitfalls in collecting, storing, and analyzing tissue and fluid samples.

Olanzapine-related fatality.

A 43-year-old male psychiatric outpatient died within hours of ingesting as much as 600 mg of olanzapine, a newer antipsychotic agent related to clozapine. Analysis of postmortem blood and urine by gas chromatography with nitrogen-selective detection yielded olanzapine concentrations of 1238 and 6987 micrograms/L, respectively, greatly in excess of levels expected following therapeutic administration of the drug. Based on the toxicology findings, the decedent's known history of suicide attempts, and the circumstances surrounding the death, this case was ruled a suicide by olanzapine overdosage.

Efficacy of two commercial products for altering urine drug test results.

OBJECTIVE: We have become aware of several commercial products that, when orally ingested, will purportedly not only eliminate "toxins" from a person's system, but will also correct any urinary imbalances caused by excessive water consumption. METHOD: Unblinded study of one volunteer subject, tested weekly x 4 for 24-hour urine elimination of test drug under conditions of control, control plus 1200 mL water, Quick Flush', and Eliminator. RESULTS: Each of the treatment protocols studied caused reductions of drug or metabolite concentrations as measured by gas chromatography-mass spectrometry in urine specimens collected up to 24 hours after ingestion of amphetamine, 9-carboxy-11-nor-delta-9-THC, benzoylecgonine, or codeine, yet the radioimmunoassay screening results demonstrated very little effect. Water alone was approximately as effective as the two commercial products in reducing the metabolite level. None of the treatment protocols employed in this study altered urinary pH, specific gravity, or creatinine concentration outside the normally accepted physiological range. CONCLUSIONS: Attempts to conceal drug abuse by water dilution are most likely to play a substantial role when concentrations are at or near the detection threshold for a particular assay such as the terminal stages of drug eliminations.

Monitoring drug use with a sweat patch: an experiment with cocaine.

Eighteen male subjects participated in a clinical study to examine a skin patch method of monitoring drug use. On the first day of each of two periods, 14 Band-aid type collection devices (sweat patches) were applied to a subject's torso, biceps, and back. On the following day, the subject took 50 or 126 mg cocaine hydrochloride intranasally. A 1-week interval separated treatment periods, and the order of dose levels was counterbalanced. On the days subjects received cocaine, one patch was removed before treatment, and five were removed after treatment. Subjects then returned over the next 7 days for removal of the remaining patches. They provided urine samples immediately after each patch removal. A group of 18 nondrug users also wore patches for up to 12 days. Analysis of the patch content yielded cocaine levels from the cocaine subjects that accurately reflected usage. Mean levels for 16 subjects were significantly different for the two treatment doses. However, given the between-dose and between-subject variability, the data cannot be used to determine either dose or time of use. The data do indicate, however, that the patch technology can be used to diagnose a single episode of cocaine use as far back as 7 days.

Driving under the influence of GHB?

A driver was found asleep behind the steering wheel of his car, and the vehicle was at rest in a traffic lane with the engine running. His manifestations included horizontal and vertical gaze nystagmus, muscle flaccidity, and severe ataxia. He admitted ingesting a white powder, which he identified as an amino acid, about 1 hour prior to discovery by police. A urine specimen collected approximately 1 hour after the traffic stop contained 1975 mg/L of gamma-hydroxybutyrate (GHB). We tentatively conclude that GHB may cause impairment of the psychomotor skills required for safe operation of a motor vehicle.

Improved long-term stability of blood cocaine in evacuated collection tubes.

A study was undertaken to determine if a relatively minor modification of our existing specimen collection tubes could enhance the long-term stability of blood cocaine. We added cocaine, benzoylecgonine (BE) and ethanol to whole sheep blood in glass tubes that were prepared to contain one of several combinations of preservatives and anticoagulant. On day 1 and at intervals of up to one year, the drugs were measured by gas chromatography-mass spectrometry (cocaine and BE) or headspace gas chromatography (ethanol). Storage of blood containing 200 ng/mL cocaine at 4 degrees C for one year resulted in 100% loss of the drug using our normal 10 mL specimen collection tubes containing 100 mg sodium fluoride and 20 mg potassium oxalate. The substitution of oxalic acid for potassium oxalate reduced this loss to 76% without any significant effect on the benzoylecgonine or ethanol concentrations. Further addition of 10 mg echothiophate iodide, a quaternary ammonium compound, brought the cocaine loss down to 60% of the original concentration by one year. Further work will be required to determine if oxalic acid and/or echothiophate iodide could be used in blood collection vials intended for forensic toxicological purposes without any detrimental effect on other assays.

On the dermal absorption of cocaine.

A 5-mg dose of cocaine free base applied to the volar forearm skin surface of a volunteer resulted in a maximal urinary benzoylecgonine concentration of 55 ng/mL at 48 h, using discrete urine specimens. A total of 58 micrograms of benzoylecgonine, representing 1.2% of the dose, was excreted in the 96-h urine. An identical trial using 5 mg of cocaine hydrochloride resulted in a maximal urinary benzoylecgonine concentration of 15 ng/mL at 24 h. We conclude that dermal absorption of cocaine represents a minor, but significant route of exposure to this drug that needs to be considered when interpreting low-level urine drug testing results.

Confirmation of LSD intoxication by analysis of serum and urine.

Serum and urine specimens of 31 patients with suspected lysergic acid diethylamide (LSD) intoxication were analyzed for LSD by both radioimmunoassay (RIA) and high-pressure liquid chromatography (HPLC). The RIA assay, using 0.1 ng/mL as the limit of detection instead of the manufacturer's recommendation of 0.5 ng/mL, was positive for LSD in 13 blood and urine specimens from 14 patients. Results were compared to HPLC analysis using methysergide instead of lysergol as the internal standard and a limit of detection of 0.5 ng/mL. HPLC detected LSD in 9 of 13 serum specimens and 11 of 13 urine specimens that had tested positive by RIA. Of 18 patients with a final clinical diagnosis of LSD intoxication, LSD was detected by RIA in 14 patients and by HPLC in 11 patients. For 13 other cases in which the final diagnosis was a condition other than LSD intoxication, serum and urine assays for LSD were negative in all cases by both techniques. LSD assays have not been generally available in clinical laboratories. We conclude that the qualitative determination of LSD in either serum or urine by a commercially available radioimmunoassay has made it possible to provide reliable laboratory confirmation of LSD intoxication.

Urinary excretion of cocaine and benzoylecgonine following oral ingestion in a single subject.

A 25 mg oral dose of cocaine HCl given to a single volunteer resulted in a peak urinary cocaine concentration of 269 ng/mL at 1 h, and a peak benzoylecgonine concentration of 7,940 ng/mL at 12 h. Urine benzoylecgonine concentrations remained in excess of 300 ng/mL for 48 h. We conclude that small, oral doses of cocaine, potentially undetectable to the user, may cause positive urine test results for at least 48 h using routine detection methods.

Effect of sodium fluoride on cholinesterase activity in postmortem blood.

Thirty-two postmortem blood specimens, with and without sodium fluoride as preservative, were analyzed for cholinesterase activity by the Michel method. The fluoridated specimens, which contained from 0.7 to 31 mg/mL (average 6.3) of sodium fluoride, were found to exhibit cholinesterase activities that were 5 to 59% (average 25%) lower than the duplicate unfluoridated specimens. We concluded that, while this decrease is quite significant, a fluoridated postmortem blood specimen may be used for the measurement of cholinesterase activity when a non-fluoridated specimen is unavailable.