Excessive fluid intake can substantially dilute urinary drug concentrations and result in false-negative reports for drug users. Methods for correction ("normalization") of drug/metabolite concentrations in urine have been utilized by anti-doping laboratories, pain monitoring programs, and in environmental monitoring programs to compensate for excessive hydration, but such procedures have not been used routinely in workplace, legal, and treatment settings. We evaluated two drug normalization procedures based on specific gravity and creatinine. These corrections were applied to urine specimens collected from three distinct groups (pain patients, heroin users, and marijuana/ cocaine users). Each group was unique in characteristics, study design, and dosing conditions. The results of the two normalization procedures were highly correlated (r=0.94; range, 0.78-0.99). Increases in percent positives by specific gravity and creatinine normalization were small (0.3% and -1.0%, respectively) for heroin users (normally hydrated subjects), modest (4.2-9.8%) for pain patients (unknown hydration state), and substantial (2- to 38-fold increases) for marijuana/cocaine users (excessively hydrated subjects). Despite some limitations, these normalization procedures provide alternative means of dealing with highly dilute, dilute, and concentrated urine specimens. Drug/metabolite concentration normalization by these procedures is recommended for urine testing programs, especially as a means of coping with dilute specimens.

Recent advances in analytical techniques have enabled the detection of drugs and drug metabolites in alternative biological specimens for the purposes of workplace testing. A wide variety of specimens are available, each providing valuable information concerning prior or current drug use. The present focus is on oral fluid (saliva), hair, and sweat. An extensive evaluation by the Division of Workplace Programs of the Department of Health and Human Services is underway to determine the utility of these specimens in federally regulated programs. In future years, the testing of alternative specimens will expand our ability to understand the patterns of drug use and will become routine in all areas of forensic toxicology.

Although many deaths occur annually from heroin intoxication, the presence of heroin has not been reported in postmortem tissues. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, extraction procedures were developed for the efficient recovery of heroin, 6-acetylmorphine, and morphine from postmortem tissue utilizing solid-phase extraction coupled with gas chromatography/mass spectrometry. From heroin-related deaths, 21 sets of blood and urine specimens were collected. The mode of death in these cases was categorized as rapid, delayed, or undetermined. Compared with delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine, and total opiates in blood; a higher ratio of free morphine concentrations to total opiate concentrations in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood of 6-acetylmorphine detection in blood; and lesser likelihood of heroin detection in urine. The study also included analysis of multiple tissue specimens from two subjects who died of heroin intoxication. Heroin was identified in urine and injection-site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen, and brain were substantially higher than in blood, liver, lung, and kidney. All specimens were positive for morphine. Heroin metabolites were detected in hair specimens. The identification of heroin and 6-acetylmorphine in biological tissues effectively established the presence of heroin in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information for the differential diagnosis of heroin-related deaths.

The stability of cocaine (COC) in blood bank blood, postmortem human whole blood, and buffers was evaluated with consideration for the presence of the degradation products, benzoylecgonine (BE) and ecgonine methyl ester (EME). At COC concentrations commonly seen, the rate of COC hydrolysis was independent of concentration. COC was stable in blood for at least 150 days if the blood was adjusted to pH 5 and preserved with 2% NaF or organophosphates and maintained at 4 degrees C or lower. Without preservation, most COC hydrolyzed to EME. The addition of a pseudocholinesterase (PChE) inhibitor without a reduction of pH caused COC to hydrolyze to BE. COC also hydrolyzed to BE in phosphate buffer. The rate of COC hydrolysis in all studies increased with increasing pH and temperature. COC was more stable in unpreserved postmortem blood than blood bank blood due to the lower pH of the former. The incubation of COC in enzyme solutions provided further evidence of the generally accepted hypothesis that COC is hydrolyzed to EME by PChE and to BE by chemical hydrolysis. In unpreserved blood, BE was more stable than EME at room temperature. There was little loss of BE or EME at refrigerated temperature over a period of 35 days and no evidence that EME or BE could be hydrolyzed enzymatically.

An oxycodone postmortem database was created from 1243 solicited cases from Medical Examiner and Coroner (ME/C) offices in 23 states in the United States over the period from August 27, 1999, through January 17, 2002. The request for cases was specific to only those cases in which the ME/C opined that the death involved oxycodone. Each case was evaluated to determine the role of oxycodone and the specific drug product OxyContin tablets in the death. Oxycodone identification was based on toxicology testing, and OxyContin identification was based on evidence found at the scene, credible witness reports, or identification of tablets in gastrointestinal contents. A system of case categorization was developed for this study based on the Drug Abuse Warning Network (DAWN) system for reporting drug abuse mortality data in the United States, using the same standardized, well-understood terminology. Of the 1243 cases, 79 cases were incomplete and could not be evaluated. There were an additional 150 cases submitted in which oxycodone was not identified by the originating ME/C. Of the remaining 1014 cases, 919 (90.6%) were related to drug abuse, whereas 95 (9.4%) cases were categorized as not involving drug abuse. Only 30 (3.3%) of the drug abuse cases involved oxycodone as the single reported chemical entity; of these, 12 cases had OxyContin identified as a source of oxycodone. Of the 919 drug abuse cases, the vast majority (N = 889, 96.7%) were multiple drug abuse deaths in which there was at least one other plausible contributory drug in addition to oxycodone. The most prevalent drug combinations were oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. Using the DAWN definitions, drug abuse cases were further categorized as drug-induced or drug-related. A total of 851 (92.6%) cases met the criteria for classification as being drug-induced, and the remaining 68 (7.4%) cases were categorized as drug-related. Cause of death (COD) statements from the originating ME/C indicated a general recognition of the role of abuse of multiple drugs in causing fatalities. Approximately 70% of the 889 cases in the multiple-drug-induced categories were listed in the COD or contributing COD statements as multiple-drug deaths. A variety of terms were employed in the COD statements to indicate multiple drug involvement such as "polydrug toxicity", "polypharmacy", "multiple drug poisoning", and "polypharmaceutical overdose". The system for death classification employed in this study recognizes the problems inherent in COD attribution when multiple drugs are involved. Use of this new system for reporting mortality data in future studies involving opioids is recommended.