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This study was designed to determine the urinary concentrations of endogenous GHB over a one-week period, the variations that occur within those concentrations, and whether those variations are affected by normalization to urinary creatinine. Its purpose was to ascertain whether endogenous concentrations fluctuate to such an extent that they may be misinterpreted as due to GHB ingestion. Every urine void produced by eight GHB-free subjects (five males and three females) over a one-week period was individually collected and analyzed for the presence of endogenous GHB and creatinine. The results of the non-normalized and normalized concentrations were statistically analyzed. Non-normalized GHB concentrations ranged from 0.00 to 6.63 µg/mL over seven days. The coefficients of variation (CV) for the individual non-normalized data were 44.0% to 77.7%. When the data were normalized to creatinine, the concentrations ranged from 0.00 to 6.79 µg/mg. The CVs for the creatinine-normalized results were between 29.7% and 76.8%. Analysis of the differences in CVs by the paired t-test (α = 0.05) found these improvements to be statistically insignificant. Such normalization allows for correction of urinary dilution or concentration by the kidneys which may affect endogenous GHB concentrations. The data also suggest significant (p < 0.001) differences in median endogenous urinary concentrations of GHB between males and females using the Mann-Whitney test. Because of the small number of subjects in this study, further investigations are required to substantiate this observation. Some of the subjects in this study demonstrated a strong tendency to produce higher or lower GHB concentrations at consistent periods during the day. This was most evident when looking at the creatinine-normalized concentrations. The results of our study indicate that there are significant intra- and interindividual variations in the urinary concentrations of endogenous GHB. Furthermore, there are also wide variations between individuals in the total daily amount of GHB excreted in the urine. Nonetheless, no specimens GHB concentration approached 10 µg/mL (non-normalized) or 10 µg/mg (normalized). This study of the variability in endogenous urinary GHB excretion supports the recommendation of 10 µg/mL as an appropriate cutoff to identify exogenous GHB exposure in the absence of rare genetic deficiencies such as GHB aciduria. Patients with such a deficiency should be readily identifiable through prominent symptoms, repeated urinalysis, or genetic testing.

The case of a 77-year-old woman who was found dead in her bathtub with her head clearly above the water line is presented. The decedent had a medical history of depression, liver disease, spinal stenosis, and diabetes mellitus. An empty medication bottle of triazolam was found in the trashcan. At autopsy, no injury or evidence of drowning was found. Toxicological analysis identified triazolam at a concentration of 0.12 mg/L in the heart blood. Triazolam and α-hydroxytriazolam were quantitated in the specimens received. The medical examiner ruled that the cause of death was triazolam intoxication and the manner of death was suicide.

This is a report of the analytical findings in 13 cases investigated by either the Office of the Chief Medical Examiner, State of Maryland or the Bexar County (San Antonio, TX) Medical Examiners Office in which citalopram, a highly selective serotonin reuptake inhibitor used therapeutically as an antidepressant, was identified. In 8 of the 9 cases in which both blood and urine specimens were received, the urine citalopram concentration exceeded the blood concentration, indicating that urine is an appropriate specimen for screening citalopram use. The average liver to blood citalopram concentration ratio was 6.5 (range 3.1–13, n = 6). Three cases had blood concentrations less than 0.24 mg/L, which is in the reported antemortem therapeutic range of the drug. Eleven cases had blood concentrations less than 1.3 mg/L; in each of these cases, citalopram was determined to be an incidental finding to the ultimate cause of death. Quantitation of citalopram and the metabolite desmethylcitalopram in these cases yielded an average parent-to-metabolite ratio of 6.4.

Ketamine, an anesthetic agent primarily used in veterinary medicine and pediatrics, continues to gain in popularity in the drug abuse scene or “Rave Wave” of all-night dance clubs. The Division of Forensic Toxicology Laboratory (Office of the Armed Forces Medical Examiner) at the Armed Forces Institute of Pathology, as the primary analytical laboratory for criminal investigative agencies in the Department of Defense (DOD), has seen requests for ketamine analysis rise from 1 in 1997 to 116 in 2000. This increasing abuse has led the DOD Urine Drug Testing Laboratories to consider adding ketamine screening to their random urinalysis program. However, before ketamine testing can be implemented as standard policy, concentrations of ketamine and metabolites in urine need to be evaluated after actual drug use. There is very little information regarding the pharmacokinetics of ketamine, especially concentrations of the drug or its two major metabolites, norketamine and dehydronorketamine, that can be expected in urine. In fact, dehydronorketamine has been believed to be an analytical artifact caused by the high temperatures of gas chromatography. In this paper, we attempt to resolve this issue with the development of a liquid chromatography-mass spectrometry (LC-MS) method. The urine concentrations of ketamine, norketamine and dehydronorketamine (presumptive) detected in 33 “positive” cases received in our laboratory since 1998 are reported. Quantitations were accomplished with LC-MS. Ketamine concentrations ranged from 6 to 7744 ng/mL. Norketamine concentrations ranged from 7 to 7986 ng/mL and dehydronorketamine (presumptive) concentrations ranged from 37 to 23,239 ng/mL.

Lamotrigine (Lamictal®) is a new anticonvulsant drug recently approved for use in the United States. Although a therapeutic range for lamotrigine has not been definitively established, a range of between 2 and 14 mg/L has been reported. Two cases are presented in which lamotrigine was identified in cases investigated by the Office of the Chief Medical Examiner, State of Maryland. Lamotrigine was identified by gas chromatography-nitrogen-phosphorus detection following an alkaline extraction. A DB-5 column provided analytical separation; no derivatization was required. Confirmation was achieved by full scan electron ionization gas chromatography-mass spectrometry. In Case 1, primidone (11 mg/t) and phenobarbital (5.5 mg/L) were found in the heart blood in addition to lamotrigine (8.3 mg/L); in Case 2, no drugs other than lamotrigine (52 mg/L) were detected in the heart blood. The peripheral blood concentration in Case 2 was 54 mg/L. The liver lamotrigine concentrations in the two cases were 41 and 220 mg/kg. The medical examiner ruled that the cause of death in Case 1 was seizure disorder and the manner of death was natural. In Case 2, the medical examiner ruled that the cause of death was lamotrigine intoxication and the manner of death was undetermined.

Chronic administration of lipophilic drugs can result in accumulation and prolonged elimination during abstinence. It has been suggested that cocaine and/or metabolites can be detected in saliva and urine for an extended period following long-term, high-dose administration. The effects of chronic oral cocaine administration in healthy volunteer subjects with a history of cocaine abuse were investigated. Subjects were housed on a closed clinical ward and were administered oral cocaine in up to 16 daily sessions. In each session, volunteers received five equal doses of oral cocaine with 1 h between doses. Across sessions, cocaine was administered in ascending doses from an initial dose of 100 mg (500 mg/day) up to 400 mg (2 g/day), increasing by 25 mg/dose/session (125 mg/session). Participation in the study was terminated if cardiovascular safety parameters were exceeded. Plasma and saliva specimens were collected periodically during the dosing sessions and during the one-week withdrawal phase at the end of the study. All urine specimens were collected throughout the entire study. Specimens were analyzed for cocaine and metabolites by solid-phase extraction followed by gas chromatographic-mass spectrometric analysis in the SIM mode. The limit of detection for each analyte was approximately 1 ng/mL. The analytes measured included benzoylecgonine (BZE), ecgonine methyl ester, cocaine, benzoylnorecgonine, norcocaine, m- and p-hydroxycocaine, and m- and p-hydroxybenzoylecgonine. Noncompartmental analysis was employed for the determination of plasma and saliva pharmacokinetic parameters. Urinary elimination half-lives for cocaine and metabolites were determined by constructing ARE (amount remaining to be excreted) plots. Two phases of urinary elimination of cocaine and metabolites were observed. An initial elimination phase was observed during withdrawal that was similar to the elimination pattern observed after acute dosing. The mean (N = 6) plasma, saliva, and urine cocaine elimination half-lives were 1.5 ± 0.1 h, 1.2 ± 0.2 h, and 4.1 ± 0.9 h, respectively. For three subjects, the mean cocaine urinary elimination half-life for the terminal phase was 19.0 ± 4.2 h. There was some difficulty in determining if a terminal elimination phase for cocaine was present for the remaining three subjects because of interference by high concentrations of BZE. A terminal elimination phase was also observed for cocaine metabolites with half-life estimates ranging from 14.6 to 52.4 h. These terminal elimination half-lives greatly exceeded previous estimates from studies of acute cocaine administration. These data suggest that cocaine accumulates in the body with chronic use resulting in a prolonged terminal elimination phase for cocaine and metabolites.