Drugs of abuse found in fatally injured drivers in Los Angeles County.

Blood or urine specimens from nearly 600 fatally injured drivers in two Los Angeles County studies were analyzed for the presence of alcohol and other drugs of abuse, including PCP, cocaine, opiates and marijuana. The results of the preliminary study indicate that 65 out of 102 fatally injured drivers had used alcohol and/or another drug of abuse - 34 had used alcohol only, 12 had used one or more other drug(s) of abuse, and 19 had used alcohol in combination with another drug of abuse. The results of the larger follow-up study, begun a year later, indicate a continued high level of both alcohol use (41.5%) and marijuana use (19%) with moderate cocaine usage (8%) and low levels (less than 2%) of barbiturate and PCP usage.

Mass screening and confirmation of codeine and morphine in urine by radioimmunoassay-GLC.

A rapid, sensitive, and specific procedure is described for the mass screening and confirmation of codeine and morphine in urine specimens. The method is sensitive to 0.5-mug/ml levels of both opiates in free and/or conjugate forms. The raw urine is screened directly by radiommunoassay, which is reactive to both free and glucuronide forms of codeine and morphine. Specimens that are screened positive are confirmed by GLC using a flame-ionization detector. The opiates are analyzed as their acetyl derivat-ves on two different columns, OV-25 and Poly-A 103. This multiple approach eliminates false positives caused by interfering substances or structurally similar compounds present in the urine.

GLC screening and confirmation of barbiturates in post mortem blood specimens.

A quantitative gas chromatographic (GC) method for the screening and confirmation of barbiturates in post mortem blood specimens is presented. Barbiturates were extracted from blood samples and the extracts cleaned-up, concentrated, and then analyzed as free drugs on a 10% UCW-982 GC column. Samples screened positive for free barbiturates were methylated to form 1,3-dimethylbarbiturates, which were then chromatographed on a 3% SE-30 column to confirm the barbiturate identity.

The determination of cocaine and its major metabolite, benzoylecgonine, in postmortem fluids and tissues by computerized gas chromatography/mass spectrometry.

An analytical procedure for the simultaneous determination of both cocaine and benzoylecgonine in postmortem fluid and tissue samples has been developed by using computerized gas chromatography/mass spectrometry and gas chromatography using a nitrogen/phosphorus (N/P) detector. Both methods are accurate and sensitive and allow the determination of tissue concentrations of cocaine and benzoylecgonine as low as 0.015 microgram/mL.

Simultaneous determination of cocaine and benzoyl ecgonine in urine by gas chromatography with on-column alkylation.

A gas chromatographic procedure has been developed for the simultaneous determination of cocaine and benzoyl ecgonine in urine specimens. The two drugs are extracted by isopropanol/chloroform from urine samples saturated with a bisalt buffer. The organic extract is evaporated to dryness, and an aliquot of the residue is injected onto the gas chromatograph to determine the presence of cocaine and the location of any extraneous peaks. Benzoyl ecgonine is then analyzed as its particular alkyl ester subject to the least interference from extraneous peaks as observed in an initial underivatized injection. The reconstituted residue is co-injected with the appropriate dimethylformamide dialkyl acetal for on-column alkylation. The use of two columns or more than one benzoyl ecgonine alkyl ester gives positive identification, and the use of isopropyl benzoyl ecgonine as an internal standard allows accurate quantification.

Rapid screening and confirmation of amphetamine, methamphetamine, methadone, and methadone metabolite in urine by gas/thin layer chromatography.

A method suitable for large scale screening and confirmation of urine speciments for amphetamine, methamphetamine, methadone, and its primary metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenlypyrrolidine) is described. The drugs are extracted from alkaline urine into an organic solvent. The amphetamine drugs are then back-extracted into a small volume of acid and identified by gas chromatography both as free bases on a 10% Apiezon L-10% KOH column and as their trifluoracetamide derivatives on a 3% OV-17 column. The organic layer, which still contains methadone and its primary metabolite, is analyzed by split-sample thin-layer chromatography using two solvent systems: ethyl acetate: methylene cloride: concentrated ammonium hydroxide (90:10:0.7) and methanol: chloroform: concentrated ammonium hydroxide (74:25:0.8). These solvent systems separate methadone from its primary metabolite without interference from other drugs or urinary substances.

Cocaine abuse and violent death.

One hundred and fourteen Los Angeles County Coroner's cases found to be positive in drug screening for the presence of cocaine were studied to determine the relationship between cocaine abuse and violent death. Of these 114 victims, 70 (61.4%) died a violent death--over 68% of these as shootings and stabbings. Fourteen of the violent death victims (20%) were found to have been behaving in a violent manner just prior to their death. Violence seems to be clearly connected to the use and abuse of cocaine.

Drug use trends among Los Angeles County probationers over the last five years.

The frequency of use of various drugs including certain opiates, diazepam, barbiturates, amphetamines, methadone, cocaine, propoxyphene, methaqualone, and phencyclidine has been determined in Los Angeles County probationers during January and February of each of the last 5 years. The results indicate that while the overall amount of drug use has decreased slightly, the frequency of use of some drugs, such as phencyclidine and cocaine, has increased greatly while the frequency of use of most other drugs, such as phenobarbital and amphetamine, has considerably decreased.

On-column gas chromatographic synthesis of 1,3-dialkyl (c = 1-10), benzyl, and cyclohexyl barbiturate derivatives.

Procedures are described for the on-column gas chromatographic synthesis of various N-alkyl-N-alkyl barbiturates where groups added to the nitrogens are benzyl, cyclohexyl, or straight chains with 1 to 10 carbons. The 1,3-dialkyl barbiturates having methyl, ethyl, n-propyl, n-butyl, cyclohexyl, isopropyl, or t-butyl groups can be prepared on-column by injecting an aliquot of a chloroform solution of the barbiturate with the appropriate N,N-dimethylformamide dialkyl acetal. The 1,3-dialkyl barbiturates where benzyl or butyl through decyl groups are added can be similarly prepared with N,N-dimethylformamide dineopentyl acetal and the appropriate alcohol to yield the desired compound. The 1-alkyl (I)-3-alkyl-(II) barbiturates where the alkyl groups differ are prepared by on-column reaction reaction of a barbiturate with aliquots of each of the respective reagents giving the desired groups.

Methaqualone RIA structure versus reactivity.

Fourteen different methaqualone-related substances (substituted 2-methyl-3-phenyl-4-quinazolinones) were analyzed by radioimmunoassay (RIA) at several different concentrations. An attempt is made to relate structural differences to the affinity of the compounds for the Roche RIA methaqualone antibody. The effects of substituent placement on the 2-methyl-3-phenyl-4-quinazolinone molecule are studied. Addition of a group to the para-position of the 3-phenyl group increased affinity, but alteration of other key functional groups had a reverse effect.

Gas chromatographic properties of 1,3-dialkyl barbiturate derivatives.

The gas chromatographic properties of 1,3-dialkyl barbiturates have been studied. The retention times for 56 different 1,3-dialkyl derivatives of both aprobarbital and phenobarbital, and for 65 different 1,3-dialkyl derivatives of secobarbital were determined by gas-liquid chromatography (GLC) using a 3% SE-30 column. Retention times were found to increase with the number of carbons added. A plot of the log of the retention time versus the number of carbons in the alkyl group added for 3-alkyl derivatives of 1-alkylbarbiturates was made for each of the three barbiturates studied. A linear relationship was found to exist for derivatives having butyl or greater groups attached to the second nitrogen of the 1-alkylbarbiturates. The slopes of the graphs for the 3-alkyl derivatives of 10 different 1-alkylbarbiturates for each barbiturate studied were all found to be identical with a similar plot for straight chain hydrocarbons. This linear relationship allowed calculation of the retention times of large N,N-dialkyl barbiturates, such as N,N-eicosanylsecobarbital, which are not readily synthesized or chromatographed.

Cocaine radioimmunoassay--structure versus reactivity.

Twenty-seven different cocaine-related substances were analyzed by radioimmunoassay (RIA) at several concentrations. An attempt was made to relate structural differences to the affinity of the compounds with the RIA benzoylecgonine (cocaine metabolite) antibody. The effects of substituent placement in the cocaine molecule were studied. Adding an alkyl group to the 2-carboxylic acid (conversion to an alkyl ester) increased reactivity, whereas changes in all other positions reduced reactivity.

Amphetamine radioimmunoassay--structure versus reactivity.

Over 60 different amphetamine-related amines were analyzed by radioimmunoassay (RIA) at several concentrations. An attempt is made to relate structural differences to the affinity of the compounds with The RIA amphetamine antibody. The effects of substituent placement in the amphetamine molecule are studied. Addition of groups to the para position of amphetamine increased reactivity whereas changes in all positions reduced reactivity.

The incidence of alcohol use in Los Angeles County homicide victims.

The blood alcohol levels were determined in 100 Los Angeles County homicide victims who died in August 1980. A total of 61% had levels of 0.01% or more. Since this percentage is substantially higher than would be expected for a cross section of the population, it appears that alcohol use is one factor that increases the chances of a person becoming a homicide victim.

Phencyclidine (PCP)-structure versus reactivity.

Seventeen different compounds having structural similarities o PCP (phencyclidine) were analyzed by radioimmunoassay (RIA) using 125I-phencyclidine reagents (Roche). Affinities were compared with molecular structures and several observations were made. It was found that the three-ring structure (1-phenylcyclo-hexylpiperidine) is essential for reactivity. Changes in and to the cyclohexyl ring and/or the piperidine ring reduced reactivity, while changes in the phenyl ring increased reactivity.

Amphetamine EMIT--structure versus reactivity.

Over 60 different amphetamine-related amines were analyzed by EMIT (Enzyme Multiplied Immunoassay Technique) at several different concentrations. An attempt is made to relate structural differences to the affinity of the compounds for the EMIT amphetamine antibody. The effects of substituent placement on the amphetamine molecule are studied. Addition of a single alkyl group to the nitrogen of amphetamine increased reactivity, whereas all other structural changes had the reverse effect, decreasing reactivity.

Urine drug testing survey and characteristics of populations of seven Los Angeles County methadone maintenance clinics.

One thousand urine samples from each of the seven Los Angeles County methadone maintenance clinics were examined for presence of drugs of abuse. The clinic populations were also concurrently studied with regard to various social factors. Significant variations which have been found among the clinics in both population characteristics and drugs detected in urine samples are discussed in the paper.

Thin-layer chromatographic screening and confirmation of methadone and its primary metabolite in urine.

A thin-layer chromatographic method for the simultaneous screening and confirmation of methadone and its primary metabolite (2-ethylidene-1,5-diemthyl-3,3-diphenylpyrrolidine) in urine specimens is presented. Urine is made basic and extracted with organic solvent. After separation and concentration, the residue is spotted, half on each of two thin-layer chromatography plates. One plate is developed in an ethyl acetate:methanol:diethylamine (90:10:1.6) solvent system and the second in an ethyl acetate:methylene chloride:propylamine (85:17:1.0) solvent system. Methadone and its primary metabolite can be detected in concentration as low as 0.5 micrograms/mL without interference from other drugs and urinary substances.

GLC/TLC analysis of codeine and morphine in urine via derivatization techniques.

A procedure has been developed for the TLC and GLC analysis of codeine and morphine derivatives in urine in cases where there is too much interference for TLC analysis as free drugs. Urine is hydrolyzed, then split into two fractions. One fraction is extracted with a polar solvent, concentrated, and acetylated. An aliquot is injected in a 3% OV-17 column and the rest is spotted on a plate developed in hexane:chloroform:diethylamine (50:30:6). The other fraction is ethylated (converting morphine to ethylmorphine), extracted with a nonpolar solvent, concentrated, acetylated, concentrated, and then spotted on a plate developed in hexane:n-butanol:acetonitrile:diethylamine (80:5:5:10). Codeine and morphine can be detected without interference at concentrations as low as 0.3 micrograms/mL.

Mass screening and confirmation of phencyclidine (PCP) in urine by radioimmunoassay/TLC.

A sensitive, rapid, and specific procedure is described for the mass screening and confirmation of PCP (phencyclidine) in urine specimens at concentrations as low as 0.3 microgram of PCP per mL. Specimens that test positive by radioimmunoassay must be confirmed by TLC using methylene chloride:n-butanol:concentrated NH4OH (85:15:0.5) as the developing solvent system. This separates PCP from other drugs or endogenous urinary substances.