Screening for drugs of abuse. I: Opiates, amphetamines and cocaine.

(1) In order to provide an efficient and reliable service for drugs of abuse screening in urine, the laboratory should analyse 20-30 samples per week, and the staff should include a scientist with special expertise in the subject. (2) Turnaround times should be between 2-3 days of sample collection. To achieve this aim it may be necessary to make special arrangements for the delivery of samples to the laboratory. Results should preferably be transmitted by electronic mail or facsimile with the necessary precautions for security and confidentiality: hardcopy reports may also be required. (3) Good communications between the requesting clinician and the laboratory are essential. An advisory service should be provided by the laboratory and clinicians should be encouraged to discuss requests and results with laboratory staff. It is important that the laboratory inform doctors of the range of substances detected and the sensitivity and specificity of laboratory assays. (4) Assays should be performed according to the manufacturer's protocols, or by modified methods that have been rigorously validated. Quality control samples should be included in each analytical run and participation in an external quality assessment scheme, e.g. UKNEQAS, is essential to provide independent confirmation and confidence that results compare with those from other laboratories. Other requirements include adequate training and supervision of staff, and careful recording of samples and results. (5) Drugs to be tested will depend on the drug 'scene' in the area but should include those drugs regularly prescribed for maintenance therapy (e.g. methadone, dihydrocodeine, benzodiazepines), and drugs frequently misused (e.g. heroin, buprenorphine, amphetamines, cocaine). (6) Positive results obtained by preliminary screening methods e.g. EMIT, should be confirmed by another analytical technique, e.g. TLC, GC or GC-MS. If there are potentially serious or legal implications, and in employment and preemployment testing, confirmation of positive results is mandatory. In some cases, e.g. checking for methadone or benzodiazepine compliance, it may be considered unnecessary to confirm positive results although possible spiking of samples cannot be excluded without checking for the presence of metabolites by a chromatographic procedure.

Heparin inactivation, acidosis and copper poisoning due to presumed acid contamination of water in a hemodialysis unit.

An accident in a hemodialysis unit involving 13 patients is reported. Circumstantial evidence suggests that acid contamination of the water supply to the unit resulted in inactivation of heparin with widespread extracorporeal clotting and secondary copper intoxication which proved fatal in one patient. Serum copper concentrations were raised in 6 of the 11 patients and whole blood copper concentrations were raised in 4 patients. Results of serum ceruloplasmin, whole blood lead and zinc analyses are reported together with tissue analyses for copper in the fatal case. The majority of the patients showed evidence of a metabolic acidosis.

Evaluation of enzymic assay for paracetamol: clinical and forensic experiences.

The performance of the enzymic paracetamol assay (Cambridge Life Science, UK) was evaluated for use in clinical and forensic analyses and compared with gas-liquid chromatography and EMIT (Syva) systems. It was found to be precise, accurate and rapid for the analysis of paracetamol in serum, with a possible application for the quantitative screening of post mortem blood.

The determination of carboxyhaemoglobin in the presence of sulphaemoglobin.

The quantitative analysis of carboxyhaemoglobin (HbCO) in fresh blood samples containing sulphaemoglobin (SHb) and in post-mortem blood samples was investigated using two automated spectrophotometers. The OSM 3 Hemoximeter gives much more accurate determinations of HbCO than the IL 282 Co-Oximeter in the presence of SHb. In addition, the OSM 3 Hemoximeter is designed to correct for the presence of SHb and turbidity of blood samples. It is thus suitable for the analysis of post-mortem samples from fire victims and decomposed bodies which may be very putrefied and contain SHb.

The analysis of lysergide (LSD): the development of novel enzyme immunoassay and immunoaffinity extraction procedures together with an HPLC-MS confirmation procedure.

A forensic procedure for the screening and confirmation of the presence of lysergide (lysergic acid diethylamide, LSD) in urine is described together with the evaluation of a novel enzyme immunoassay (EIA) and immunoaffinity extraction procedure. Following initial screening using either an established radioimmunoassay (RIA) or a novel EIA procedure, a quantitative estimate is established using a conventional high performance liquid chromatography-fluorescence (HPLC) technique following solid phase extraction. Final confirmation and quantitation, without derivatization, is established using HPLC in combination with electrospray ionization (ESI) mass spectrometry using methysergide as an internal standard. The detection limit of LSD in urine is 0.5 ng/mL. A blind trial confirmed the validity of the results. The choice of internal standard is discussed. Consideration is given to the photosensitivity of LSD solutions. A study of potential interferants in the HPLC-MS confirmation of LSD is presented and shows that for the wide range of compounds studied, there are none that would interfere with this confirmation technique. A comparison is shown between solid phase and immunoaffinity extraction/clean up procedures, and between RIA and EIA screening procedures.

Diazepam in the treatment of dyspnoea in the 'Pink Puffer' syndrome.

Diazepam, in moderate doses, has been used in a placebo controlled, single blind study to treat dyspnoea in four patients severely disabled from chronic airflow obstruction. The subjects had the 'pink puffer syndrome', usually associated with emphysema and were not hypercapnoeic nor severely hypoxic at rest. With diazepam, they experienced a striking reduction in dyspnoea, and an improvement in effort tolerance; in addition the slope of the ventilation/CO2 response curve was reduced. There were no changes in resting blood gases. Psychiatric examination at the end of the study did not reveal prominent anxiety, although three patients were depressed. The use of diazepam to treat dyspnoea in this syndrome is safe in the absence of any acute infection

Bioavailability of lithium carbonate and lithium citrate: a comparison of two controlled-release preparations.

The pharmacokinetics of two marketed controlled-release lithium preparations, lithium carbonate ('Priadel') and lithium citrate ('Litarex'), were compared in 5 normal volunteers in a crossover design using identical doses (27.2 mmol lithium). Although the total bioavailability of the two preparations was similar, the peak serum lithium achieved was significantly lower with the lithium citrate than with the lithium carbonate preparation.