Eye malformations in rats: induction by prenatal exposure to nickel carbonyl.

Exposure of pregnant rats to inhalation of nickel carbonyl on days 7 or 8 of gestation frequently causes the progeny to develop ocular anomalies, including anophthalmia and microphthalmia. The incidence of extraocular anomalies is very low. The specificity of nickel carbonyl for induction of ocular anomalies in rats appears to be unique among known teratogenic agents.

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.

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.

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.

Markedly prolonged theophylline half-life in liver failure.

Theophylline toxicity developed within 48 hours of admission in a 63-year-old alcoholic male who presented with shortness of breath, edema, and lethargy. Using liquid chromatography, a serum theophylline half-life of 134 hours was observed following discontinuation of the drug. This report emphasizes the effect of hepatic disease on theophylline clearance and the need for frequent monitoring of plasma theophylline concentrations in cirrhotic patients.

Blood and urine concentrations of cyclizine by nitrogen-phosphorus gas-liquid chromatography.

Gas-liquid chromatography with nitrogen-phosphorus detection was used to analyze blood and urine from a volunteer who ingested 50 mg of cyclizine hydrochloride. A peak blood cyclizine concentration of 69 ng/mL was observed 2 hr after drug administration, and the levels declined thereafter in a biphasic manner, with estimated half-lives of 7 and 24 hr for the early and late phases, respectively. The peak urine cyclizine concentration of 12.5 ng/mL was achieved at 4 hr after administration; only 0.01% of the dose was excreted in the 24 hr urine. Norcyclizine was not observed in blood or urine; however, the detectability of the method for this metabolite is poor relative to the parent drug.

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.

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.

Detection of phencyclidine usage by radioimmunoassay of saliva.

Paired serum and saliva samples, obtained from 100 emergency department patients suspected of phencyclidine (PCP) intoxication, were analyzed using a specific PCP radioimmunoassay (RIA). Seventy-four of the 100 saliva samples and 75 of the paired serum samples were positive for PCP. The final clinical diagnosis was PCP intoxication in 79 cases. Of these, both serum and saliva tests were positive in 70 cases, only serum was positive in two cases, and both serum and saliva samples were negative in seven cases. The concentration of PCP in the samples did not correlate with the severity of PCP intoxication. In the remaining 21 cases, with no clinical evidence of PCP intoxication, PCP assays were negative in both serum and saliva in 17 cases, three patients had positive saliva and serum tests, and one other patient had a positive PCP saliva assay. Thus, saliva would appear to be as reliable as serum as a specimen for PCP analysis.

Comparison of 3H- and 125I-radioimmunoassay and gas chromatography/mass spectrometry for the determination of delta 9-tetrahydrocannabinol and cannabinoids in blood and serum.

Blood and serum specimens from 100 subjects in a driving study were tested for the presence of delta 9-tetrahydrocannabinol (THC) by 3H- and 125I-labeled RIA and GC/MS. The specimens were also analyzed for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol by the two RIA methods. Blind quality control specimens containing THC were included with each batch of subject specimens and sent coded to three participating laboratories. The methods were assessed for accuracy, reproducibility, detectability, specificity, and the results correlated. It was found that serum was a better matrix than blood for determination of cannabinoids. The three methods gave parallel but significantly different quantitative results, apparently due to calibration problems. However, each technique was capable of measuring THC concentrations up to three hours after usage.

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.

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.

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.