Importance of evaporation conditions and two internal standards for quantitation of amitriptyline and nortriptyline.
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Biomedical subjects
Publications and source records attributed to B S Finkle.
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A total of 1859 cases provides the basis for this study in which propoxyphene, and often its major metabolite, was demonstrated by toxicological analysis in the blood or tissues of the deceased at 27 medical examiner or coroner's offices across the United States and Canada. The study period includes the last five months of 1975 through December 1978. The cases describe a clearly defined adult population with a marked tendency toward hypochondria, chronic minor illness, and severe psychiatric problems. The high proportion of suicides (44.1% of the total cases and 54.0% of the drug-caused deaths) and multiple-drug toxicities (88.6%) suggests that the involvement of propoxyphene in many of these fatalities may be of less significance than the phenomenon of "polypharmacy" and self-medication without appropriate medical supervision. This evaluation of propoxyphene provides no evidence that propoxyphene is responsible for "street-drug" fatalities. Its appearance in postmortem toxicological examinations has been declining sharply since 1977, but it continues to be dangerous when used excessively, particularly in combination with alcohol and other central nervous system depressant drugs.
This study describes a population of deceased persons in which death was generally caused by ingestion of numerous drugs, of which diazepam was only one agent. This drug occurred with high frequency relative to the total case load at each site, but its toxicological importance was often of a low order, and its role in the fatal cases was judged as minimal.
A simple, isocratic, reversed-phase, high-pressure liquid chromatographic procedure was developed for the determination of chlordiazepoxide and its major metabolites in plasma and urine. The within-run coefficient of variation was 3.4-8.0%, and the day-to-day variation was 4.0-8.0%. Recoveries of 80-91% with sensitivity limits of 50 ng/ml were obtained for the parent drug and its metabolites. Plasma and urine samples collected after single intravenous and single oral doses were analyzed using this procedure.
1-alpha-acetylmethadol (LAAM) is a new drug under development for the treatment of heroin dependence. A new analytical method applicable to the accurate biodispositional study of the drug and its metabolities is described and critically discussed in this report. The procedure involves sample preparation and direct organic solvent extraction using eta-butyl chloride, amide derivatization by molecular rearrangement, and gas chromatography-chemical ionization mass spectrometry-selected ion monitoring, with methane as the carrier and ammonia as reagent gases. Deuterated (d3 stable isotopes of LAAM and its metabolites are used as internal standards. The method is free from qualitative interferences and has quantitative sensitivity to 5 ng/ml for 2.0 ml samples with 10-15% accuracy and precision in the range 5-100 ng/ml; and 2-5% at concentrations up to 750 ng/ml. Specimens of plasma, whole blood, urine, bile, brain, liver, and other visceral samples have been successfully analyzed, as well as in vitro preparations such as hepatic microsomes. By appropriate data processing, the method lends itself to routine analysis and high volume work; even manually the method is capable of at least 50 samples per week. A simplified procedure for the analysis of LAAM and its metabolites in urine only is also presented and discuet up and use the methods.
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Eighteen medical examiners, coroners, and forensic science laboratories and offices, representing a total jurisdictional population of 52.6 million, were visited during November 1975, and more than 1200 cases occurring in the four years from 1972 through 31 July 1975 were evaluated for inclusion in the study. The sites were distributed across the United States and Ontario, Canada, and included urban and rural, states, city, and county jurisdictions. Scientific data and circumstantial information was gathered consistently for each case and site by means of five questionnaires. Finally, 1022 cases were compiled and examined, and the data were analyzed to form the body of data from which this report is written. The following conclusions may be drawn. 1. The number of deaths involving propoxyphene is increasing each year, and at a faster rate than total drug deaths. The absolute numbers and rate are different in urban and rural areas, but the frequency reached 6.0 deaths per million population in 1974. Deaths attributed to suicide as well as those determined to be accidental deaths and undetermined have increased. 2. Approximately 66% of all the cases studied had the word propoxyphene included in the cause of death statement on the death certificate. Approximately 46% of the cases were classified as suicide (64% of them female and 36% male), 26% as accidents, and 21% as undetermined. 3. The deceased were mainly middle-class, Caucasian, urban dwellers, with male and female evenly distributed. Their ages were from 20 to 50 years, with few outside this range. Female ages were uniformly distributed, but males in their early twenties were very prominent. This is different from the U.S. population age distribution, which is currently dominated by teenagers. Propoxyphene does not appear to be a pediatric problem, as seen in the study. 4. The deceased were not part of the illegal drug abuse population and had no particular propensity for the use of heroin or narcotics, but rather they were a particular medical population of those who misuse prescription drugs and alcohol. 5. The deceased did have a marked tendency to hypochondria, chronic minor illnesses and emotional problems. Some 43% had recent medical histories, and 82% had a documented psychiatric history which often included (51%) self-destructuve behavior such as suicide attempts. Almost all received a wide range of prescription drugs, particularly tranquilizers, which they often misused in the sense of self-medicating, multiple drug ingestion, and combining alcohol with their medication. Approximately 34% had a history of misusing some drug, and 20% could be defined as abusers in that they were prone to excessive use of their medications; 44% had diazepam available to them, and 17% were either problem drinkers or alcoholics.
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