Faculty Bibliography

Oral fluid has become a widely accepted alternative matrix for drugs of abuse detection. Immunoassays have been developed for on-site testing of cocaine and metabolites in oral fluid. The performance of the Cozart RapiScan Oral Fluid Drug Testing System (CRS) was evaluated in comparison with Cozart Microplate Enzyme Immunoassay Cocaine Oral Fluid Kit (COC ELISA) and gas chromatography-mass spectrometry (GC-MS) at several screening and confirmation cutoffs, including those proposed by SAMHSA and those currently in use in the U.K. Oral fluid samples (n = 1271) were collected prior to and following controlled clinical cocaine administration. CRS provides a qualitative screen at a preset cutoff of 30 microg/L. Sensitivity, specificity, and efficiency for CRS (30 microg/L) as compared with COC ELISA with a cutoff of 30 microg/L were 92.1%, 91.8%, and 92.0%. The comparison of CRS (30 microg/L) with the 8-mg/L proposed SAMHSA confirmation cutoffs for cocaine and/or benzoylecgonine exhibited a sensitivity of 82.7%, a specificity of 94.5%, and an efficiency of 87.6%. For this study, an alternative CRS cutoff of 20 microg/L was also evaluated. Performance characteristics of CRS (20 microg/L) at the proposed SAMHSA confirmation cutoffs were 89.9%, 89.7%, and 89.8%, respectively. At cutoffs in use in the U.K., 30- micro g/L CRS screen and 15- microg/L GC-MS cutoffs for cocaine, benzoylecgonine, and/or ecgonine methyl ester sensitivity, specificity, and efficiency were 89.4%, 92.2%, and 90.7%, respectively. Cozart RapiScan had performance similar to the COC ELISA assay for the detection of cocaine exposure and suitable sensitivity and specificity at the proposed SAMHSA cutoffs.

BACKGROUND: Oral fluid is currently being evaluated as an alternative matrix for monitoring illicit drugs in federally mandated workplace drug testing, for addiction treatment programs, and for driving under the influence testing. The sensitivity, specificity, and efficiency of the Cozart Microplate EIA Cocaine Oral Fluid Kit (COC ELISA) were determined by comparison with gas chromatography-mass spectrometry (GC/MS) results at screening and confirmation cutoffs proposed in the US and UK. METHOD: Oral fluid was collected by expectoration after citric acid candy stimulation or with Salivette neutral cotton swabs or Salivette citric acid-treated cotton swabs before and after cocaine (COC) administration. Specimens (n = 1468) were analyzed with the COC ELISA for screening and with solid-phase extraction followed by GC/MS for confirmation. Three screening cutoffs (10, 20, and 30 microg/L) and four GC/MS cutoffs (2.5, 8, 10, and 15 microg/L COC, benzoylecgonine, and/or ecgonine methyl ester) were evaluated. GC/MS limit of quantification was 2.5 micro g/L for all analytes. RESULTS: COC ELISA interassay imprecision (CV; n = 19) was 16% at 16.7 microg/L and 12% at 81.8 microg/L. With the 2.5, 8, 10, and 15 microg/L GC/MS cutoffs, 59.0%, 54.7%, 52.7%, and 48.7% of the oral fluid specimens were positive, respectively. Sensitivity, specificity, and efficiency were 92.2%, 84.7%, and 88.8%, respectively, for the suggested Substance Abuse and Mental Health Services Administration (SAMHSA) cutoffs and 90.2%, 89.2%, and 89.7% for cutoffs currently used in the UK. CONCLUSIONS: COC ELISA had suitable sensitivity, specificity, and efficiency for identifying COC exposure at both the proposed SAMHSA and UK cutoffs. Sensitivity, specificity, and efficiency were >84% for both cutoffs, but 92 additional true-positive samples were identified with the SAMHSA cutoffs.

AIMS: To determine the incidence of methadone as either the principal cause of death or as a contributing factor in drug related deaths in the Strathclyde Police region of Scotland and to assess the impact of supervised consumption of methadone on the number of deaths that occurred within each health board area within this region. DESIGN: Retrospective analysis of records held within the Department of Forensic Medicine and Science based at the University of Glasgow over the 11-year period 1991-2001. SETTING: The Strathclyde Police region of Scotland (population approximately 2.25 million). FINDINGS: In 1991, there was one death recorded which was attributable to methadone. Following the introduction of the methadone maintenance programme (MMP) in Glasgow during 1994, there was a 100% increase in these deaths compared to the previous year, a trend which continued over the subsequent 2 years. Following a confidential enquiry into these deaths and a greater compliance from pharmacies supervising methadone consumption, deaths involving methadone had decreased by 48% in 1997. This was particularly evident in the Greater Glasgow Health Board Area, where methadone prescribing has continued to rise annually. However, some difficulties still exist. Multiple take home doses are sometimes prescribed when a pharmacy is closed, which may lead to inadvertent overdose or facilitate diversion of legitimate supplies. In addition, continued use of heroin was found in approximately one-fifth of MMP patients, suggesting possible underdosing. CONCLUSIONS: A growing prevalence of heroin misuse has resulted in an increase in the number of individuals entering the MMP. Despite a continuing increase in the amount of methadone prescribed, methadone deaths in Strathclyde have decreased since 1996 due possibly to changes in both prescribing and clinical care. With efficient management to establish that the patient is complying with the guidelines of the programme and has stopped heroin misuse, methadone can be a safe drug for substitution therapy.

The aim of the study was to compare self reported "ecstasy" use with the results of the analysis of hair harvested from the same users. Subjects were recruited by multisite chain-referral sampling within the 1994-95 "dance scene" in Glasgow. One hundred subjects donated hair after completing a lengthy interviewer-administered questionnaire. Overall gross concordance between self reported "ecstasy" use and discovery of MDMA (or related compounds) in analysed hair did not surpass 59%, and no relationship had a Cohen's kappa of more than 0.08. Within the positive concordant dataset (n = 52), scatter was considerable, with no correlation being significant, and none more strongly positive than -0.0518. The results presented here indicate that, as far as MDMA is concerned, if judged by self-report, hair does not reach a level of apparent accuracy that would permit its use as a general population estimator. However, hair testing is probably more reliable than self-report, and its accuracy could be verified independently if large-scale inter- and intra-laboratory comparative research is conducted.

Drug use histories were collected from 100 subjects recruited from the "dance scene" in and around Glasgow, Scotland. In addition, each subject donated a hair sample which was analyzed by gas chromatography/mass spectrometry (GC/MS) for amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MD MA) and 3,4-methylenedioxyethylamphetamine (MDEA). The hair samples were analyzed in two 6 cm segments or in full, ranging from 1.5 to 12 cm depending on the length of the hair. Approximately 10 mg of hair was ground to a fine powder before treatment with beta-glucuronidase/aryl sulfatase. A solid-phase extraction procedure was carried out followed by derivatization with pentafluoropropionic anhydride (PFPA). All extracts were analyzed by gas chromatography/mass spectrometry (GC/MS). Of the 139 segments analyzed, 77 (52.5%) were positive for at least one of the five amphetamines. The drug concentrations found in the hair were compared with the self-reported drug histories. A concordance of greater than 50% was found between the self-report data and levels detected in hair. However, no correlation was found between the reported number of "ecstasy" tablets consumed and the drug levels detected in hair. An increase in the average drug levels measured was observed from low to high use (number of "ecstasy" tablets/month). A large number of false negatives and a low number of false positives were observed.

There was a substantial increase in the percent of drug screens testing positive for methadone between 1991 and 1996 in the Strathclyde region of Scotland. Seventy-nine per cent (n = 136) of these deaths were drug-related, involving methadone either alone or in combination with other drugs such as diazepam, temazepam, alcohol and morphine. The involvement of methadone in the majority of these fatalities was due to diversion of legitimate supply. This paper highlights the dangers of resuming methadone consumption following a period of abstinence or when taken in combination with other drugs.

A solid-phase extraction (SPE) method for the efficient extraction of methadone and its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline, from whole blood is described. The procedure combines extraction on Isolute Confirm HCX mixed-mode SPE columns and gas chromatographic-mass spectrometric analysis with deuterated methadone as the internal standard. The optimum extraction conditions for all three analytes were determined using spiked whole blood. The developed method is easier and faster than current liquid-liquid extraction (LLE) procedures and produces cleaner extracts. Calibration curves were linear from 0 to 600 ng/mL (r2 > 0.99) with recoveries greater than 90% for all three analytes. The concentrations of methadone and its metabolites in postmortem blood were determined in fatal cases using the developed SPE method and were found to compare well with results obtained using LLE.