Comparison of a TLC method with EMIT and GC/MS for detection of cannabinoids in urine.

Urine specimens were analyzed in parallel with a new TLC method, an EMIT assay, and a reference GC/MS method. At a 9-carboxy-THC cutoff of 20 ng/mL, the TLC method correctly identified 92% of the positive urines and 97% of the negative urines. In contrast, only 63% of the urine specimens shown by GC/MS to contain greater than 20 ng/mL of 9-carboxy-THC were identified as positive by the EMIT d.a.u. assay at the 100-ng/mL cannabinoid cutoff.

A comparison of post-mortem ethanol levels obtained from blood and subdural specimens.

Post-mortem subdural ethanol levels have been proposed as a useful test in certain forensic cases involving head trauma, particularly when the time interval from injury to death may have caused a lowering of the blood ethanol concentration to insignificant or undetectable levels. This study of 75 autopsied persons from whom both blood and subdural ethanol levels were obtained, shows the usefulness of the subdural ethanol level, especially where there is a prolonged or unknown post-traumatic time interval. Use of such a test is recommended in these situations.

Preliminary tests for drugs of abuse.

A drug-testing program must be designed by the client in consultation with the laboratory. The test procedures selected for the analytes in question depend on the defined "cutoff" concentrations, equipment available, and turnaround time. Preliminary tests are needed to separate the large number of negatives from presumptive positives, which then have to be confirmed. Immunoassays done with random-access analyzers are the procedures of choice. In clinical situations, thin-layer chromatographic procedures may be favored. The attributes and liabilities of the various procedures are presented as guides to the selection of a suitable procedure for a particular client.

Role of the toxicology laboratory in suspected ingestions.

The toxicology laboratory can fill an important role in improving patient care. Whether the service provided by the laboratory is specifically in support of a pediatric population or devoted more to the entire hospital population, the considerations involved in its configuration are the same. These considerations involve establishment of an open dialogue between the laboratory and clinical staff, an integrated and comprehensive analytic approach, and provision of reliable laboratory data in a timely fashion.

Role of the toxicology laboratory in the treatment of acute poisoning.

The modern toxicology laboratory can play an important role in the evaluation of poisoning. In order to appreciate the nature and extent of this role, several essential elements necessary to an acute care toxicology service should be considered. When an ongoing and effective dialogue between clinicians and the toxicology laboratory staff is established, and a broadly based analytical approach is applied to the analysis of the appropriate biological fluids, a dynamic and viable toxicology service will result. How these elements work together to facilitate this service will be discussed, based primarily on experience in a large teaching hospital. This experience indicates that if the elements necessary to provide laboratory support in the investigation of an alleged poisoning are in place, the toxicology laboratory plays an important role in ensuring optimum and effective patient care.

Testing for basic drugs in biological fluids by solvent extraction and dual capillary GC/NPD.

Basic drugs were extracted from 1 mL of serum, urine, or other biological fluids under alkaline conditions into hexane:isoamyl alcohol (98:2). The drugs were back-extracted into acid and re-extracted into 50 microL of chloroform:isoamyl alcohol (95:5) after the acid had been alkalinized. An aliquot of the chloroform:isoamyl alcohol was injected onto a temperature programmed gas chromatograph equipped with two nitrogen phosphorus detectors and two fused silica capillary columns fitted into a single injector. Results obtained from 388 serum samples (from suspected overdose patients) tested using this procedure are presented. The same extraction applied to a variety of body fluids proved reliable for quantitations of several of the basic drugs when a packed column was used.

Detection and confirmation of urinary cannabinoids.

Both a thin layer chromatographic procedure (TOXI-LAB) and two homogeneous immunoassays with differing sensitivity limits (EMIT-st, and EMIT d.a.u.) were used to test 525 urine specimens for metabolites of tetrahydrocannabinol. Negative results were obtained by all techniques for 283 specimens. The EMIT-st was positive for 184 specimens, the EMIT-d.a.u. for 47 additional specimens. The TOXI-LAB results were positive for all these 231 specimens. An additional 11 specimens were positive by EMIT-d.a.u. and negative by TOXI-LAB. Gas chromatography/mass spectrometry analyses of five of these 11 indicated that their average 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid concentration was 7.4 +/- 2.2 ng/mL, well below the lower detection limit of the TOXI-LAB procedure. Using both EMIT-d.a.u. and TOXI-LAB assures a reliable urinary cannabinoid analysis above a concentration of 25 ng/mL.

Acute ethylene glycol poisoning.

Ethylene glycol, a major constituent of antifreeze, is metabolized by alcohol dehydrogenase to glycoaldehyde, glycolate, glyoxylate, and oxalate. The metabolites of ethylene glycol cause severe metabolic acidosis and central nervous system, pulmonary, and renal damage. Ethanol competes with ethylene glycol as an alternate substrate of alcohol dehydrogenase. Two cases of ethylene glycol poisoning associated with serum concentrations of 59 and 150 mg/dl are reported. One patient was protected from the toxic effects of the metabolites because of concomitant ethanol ingestion. In patients with unexplained anion and osmol gaps, early diagnosis and therapy with ethanol and hemodialysis help prevent the toxic manifestations of ethylene glycol poisoning.

Homogeneous enzyme immunoassay of acetaminophen in serum.

A new commercially available homogeneous enzyme immunoassay, using the glucose-6-phosphate dehydrogenase (G6PDH) catalyzed conversion of NAD to NADH, has been evaluated and applied to the determination of acetaminophen in serum. Replicate analysis of serum control samples over the range of 10-200 micrograms/mL demonstrated a within-assay coefficient of variation of less than or equal to 4.6% and a between-assay coefficient of variation of less than or equal to 5.8%. Regression analysis of two separate groups of 98 and 47 serum samples by this technic, using different reagent lots, and a HPLC reference method gave equations of y = 0.981x - 0.941 (r = 0.984) and y = 1.06x - 2.21 (r = 0.994), respectively. No interference due to hemolysis or turbidity was noted. Evaluation of samples containing 35 commonly prescribed or over the counter medications demonstrated no significant cross-reactivity. Prepared reagents were stable over a period of at least 2 months when stored at 4 degrees C. Correlations between two reagent lots were excellent (r = 0.998). A single sample can be analyzed expeditiously. The result may help evaluate a potential acetaminophen poisoning. Another way to assess this toxicity, calculation of the elimination half-life, has limitations that depend on the precision of the analysis.

Combined enzyme immunoassay-LCEC method for the identification, confirmation, and quantitation of opiates in biological fluids.

An enzyme multiplied immunoassay technique (EMIT) was used to test for opiates (morphine, hydromorphone, and codeine) in extracts of blood, bile, and tissue homogenates. All immunoassay opiate positive specimens were then tested by a reversed-phase liquid chromatographic procedure using electrochemical detection (LCEC). Blood specimens were then quantitated by LCEC. The sensitivity of the immunoassay (as morphine) was 0.020 mg/L, 0.200 mg/L, and 0.100 mg/kg for blood, bile, and tissue homogenates, respectively, with 2% intrarun and 7% interrun precision. The LCEC method was linear from 0.005 to 0.300 mg/L for morphine, hydromorphone, and codeine (nalorphine internal standard) with detection limits of 0.005 mg/L for each analyte. Intrarun and interrun precision varied from 1 to 2% and 6 to 11%, respectively. Recoveries, using a double extraction technique, ranged from 70 to 95%. These two methods, applied to 495 post mortem cases, demonstrated a 6% incidence of opiates, with no false positives.

The role of the toxicology laboratory in emergency medicine.II: Study of an integrated approach.

The utility of the toxicology laboratory in emergency medicine is directly related to both establishing communication between the toxicology laboratory and the clinical staff, and to providing reliable toxicology data while the diagnostic process is still in progress. When 604 patients, on whom a "complete toxicology screen" was requested, were evaluated using qualitative probes involving chemical spot tests, immunoassay, TLC and/or selected GC/HPLC methods, the resulting data were demonstrated to be of value. The ability of the clinician to accurately predict which, if any, of a large number of intoxicants were present in a given patient, was found to be minimal and as a result these combined tests were found to be essential in facilitating a proper diagnosis. Additionally, it was found that using only chemical spot tests, immunoassay and TLC in a combined qualitative approach detected 94-98% of all the substances eventually found within the population when it was further studied using more sophisticated instrumental methods. The integrated approach involving the initial establishment of a dialogue between the clinician and the toxicologist, use of simple qualitative analytical probes, confirmation of positive findings and prompt reporting of toxicology data is a viable way in which meaningful toxicology support can be provided while the diagnostic process is still underway.

Dr. Alexander O. Gettler's documentation of a radiation hazard.

An example of the forensic scientist's role in the confirmation and subsequent eradication of a most lethal occupational hazard is discussed. the active participation of Dr. Gettler in the detection of radioactive substances in the watch dial industry lead to the removal of this hazard and a healthier work place.

A fatal chlordane poisoning.

Chlordane was, prior to regulatory action by EPA in 1976, an extensively used insecticide for both household and agricultural pest control purposes. It was readily available to the general public for many years; thus, human exposure, including poisonings, has been documented. A case reporting fatal chlordane ingestion with residue levels in various body tissues is presented. Analyses were performed by gas-liquid chromatography. The highest residue levels were reported in stomach contents, liver, brain, and adipose tissue.

EMIT-st screening for drugs of abuse: methaqualone.

The Emit-st (single test) drug detection system was determined, for methaqualone and several of its metabolites, to be reliable and simple to perform. Its sensitivity was 0.3 micrograms/mL for methaqualone and 0.4 micrograms/mL for the only methaqualolne metabolite (4-hydroxymethaqualone) known to be excreted unconjugated. This assay also detects mecloqualone, a Schedule I drug marketed in Europe and South Africa.

Acute loxapine intoxication in a child.

Thin-layer chromatography (TLC) was used to confirm the alleged ingestion of Loxitane (loxapine succinate) by a 20-month-old child. GC was used to further characterize TLC spots and to quantitate the loxapine concentration of the blood at 0.072 mg/dL, which was consistent with the child's presenting signs of lethargy and ataxia. The appropriate supportive symptomatic therapy, with monitoring for CNS and cardiovascular toxicities, resulted in an uneventful recovery.

The role of the toxicology laboratory in emergency medicine.

The toxicology laboratory can provide diagnostic and prognostic information relevant to an alleged acute poisoning. To do this effectively, the clinician must cooperate by providing suitable specimens to and dialogue with the laboratory. The many simple laboratory tests that enable prompt qualitative results relevant to diagnosis as well as those more elegant procedures required for prognosis are briefly described. The toxicologist, by promptly reporting the results of these tests to the clinician and assisting in their interpretation, helps insure optimal patient care.