Drug screening in an unconventional matrix: hair analysis.
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Biomedical subjects
Publications and source records attributed to D N Bailey.
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Cocaine- and methamphetamine-related homicides and fatal accidental overdoses in San Diego County were studied retrospectively for the 1987 calendar year. Cocaine was involved in 66 cases (39 homicides, 27 accidental overdoses), methamphetamine in 32 cases (23 homicides, 9 accidental overdoses), and a combination of cocaine and methamphetamine in 10 cases (4 homicides, 6 accidental overdoses). The composite for cocaine-related deaths was a 30-year-old black man in whom was also found at least 1 other drug, usually ethanol or morphine. The composite for methamphetamine-related deaths was a 32-year-old Caucasian man who used methamphetamine with at least 1 other drug (usually ethanol). For cases involving both cocaine and methamphetamine, the composite was a 36-year-old Caucasian man in whom was also found at least 1 other drug, usually ethanol, codeine, or morphine. Mean tissue concentrations of cocaine and benzoylecgonine were significantly higher in accidental overdoses than in homicides except for cocaine concentrations in liver, which did not differ significantly between the two groups. For methamphetamine-related deaths there was no significant difference between mean tissue concentrations in accidental overdoses and in homicides. Cocaine or methamphetamine or both were involved in approximately one third of homicides in San Diego County in 1987, and when fatal accidental overdoses were included, cocaine was involved in twice as many cases as methamphetamine.
The stability of therapeutic concentrations of 11 drugs (amikacin, carbamazepine, digoxin, gentamicin, lithium, methotrexate, phenobarbital, phenytoin, quinidine, theophylline, tobramycin) and two trace elements (copper and zinc) in plasma stored in serum separator ("Corvac" brand) blood collection tubes was investigated over a 1 week period of storage in the refrigerator. No significant change in concentration was noted for any analyte during the study period. Concentrations were also not significantly different from those observed during concurrent storage of the same plasma samples in nonserum separator ("Vacutainer" brand) blood collection tubes.
The frequency of detection of cocaine and/or its major metabolite, benzoylecgonine, during toxicology screening of a university medical center patient population was evaluated by retrospective review of the results of the 2,200 toxicology screens performed during 1986 on either urine or urine in conjunction with blood. Of these screens, 234 (10%) were positive for cocaine and/or its metabolite--a substantial increase from the 1% noted for the year 1978 at this medical center. Men and women were represented equally with the most common age range being 21 to 30 years for both. Most adults (64%) were located on either the obstetrics or the trauma services. In 37 instances cocaine was detected in neonates, presumably due to transplacental transmission. Cocaine and/or its metabolite were found either alone or in combination with other drugs with about equal frequency. The most common other drugs were ethanol, morphine, amphetamine, methamphetaine, and phencyclidine. Cocaine detection increased throughout the study period with 68% of positives occurring from July through December 1986. Analysis of cocaine and/or benzoylecgonine should be an integral part of toxicology screening performed on a university medical center patient population.
The frequency of detection of "amphetamines" (amphetamine and/or methamphetamine) in the toxicology tests of a university medical center patient population was evaluated by retrospective review of the results of 2,900 toxicology test profiles performed on urine during the year 1986-87. Ten percent of these (291 cases) were positive for either amphetamine alone or amphetamine in conjunction with methamphetamine--a substantial increase from the 3% noted in 1978 at this medical center. Amphetamines were detected predominantly in males (164 cases). The most common age range for the entire series was 21 to 30 years (61% of cases). The typical user was a 27 year old Caucasian man who used amphetamines alone or in combination with at least one other drug with about equal frequency. The sympathomimetic amines (ephedrine, phenylpropanolamine, and pseudoephedrine) were the most frequently associated category of other drugs, perhaps reflecting either adulteration of the amphetamines with these compounds or concurrent ingestion of over-the-counter preparations containing these agents. Requests for those toxicology tests which subsequently revealed amphetamines mostly originated in the emergency room (30% of cases) although 25% originated on the trauma service and 17% on the obstetrics service. Twelve percent of cases occurred in neonates, presumably reflecting transplacental transmission of amphetamines detected in mothers that were studied simultaneously. Amphetamine and methamphetamine were detected together 84% of the time. Analysis of amphetamines should be an integral part of toxicology testing performed on a university medical center patient population.
The rate of detection of phencyclidine during toxicology testing of a university medical center patient population was studied by retrospective review of the results of 6,870 toxicology panels performed on urine during the period September 1, 1984 to September 1, 1987. The rate was compared with that noted in earlier studies of drug detection at this institution. For the three-year period, 91 panels (1.3%) involving 82 individuals were positive for phencyclidine: men, 49 cases; women, 15 cases; children, 10 cases; and neonates, 8 cases. The typical user was a 25 year old Hispanic or Black man who had ingested phencyclidine alone or in combination with at least one other drug (usually ethanol or cocaine) and who had been admitted to the trauma service. Despite use of the same analytical methodology and increased ordering of toxicology tests during the study period, the frequency of phencyclidine detection decreased during each year of the study (1984-85, 2.3% of 1,280 panels; 1985-86, 1.5% of 1,956 panels; and 1986-87, 0.9% of 3,634 panels). These figures are substantially lower than the 5% rate noted in our study of emergency room patients in 1979. These data suggest that the use of phencyclidine may be decreasing, possibly due to increase in abuse of other drugs such as cocaine and the amphetamines and to the more stringent restrictions placed upon phencyclidine synthesis. About half of the phencyclidine-positive findings occurred in trauma patients, suggesting the particular importance of searching for the drug in this population.
The effect of parenterally administered atropine on the previously demonstrated percutaneous absorption of phencyclidine and methadone was investigated in vivo using the hairless (SKH, hr-1/hr-1) mouse as an experimental model. At both three hours and four hours following topical application of aqueous phencyclidine hydrochloride, the mean drug concentration in liver was significantly lower in mice that had received atropine sulfate by intraperitoneal injection than in mice that had received only water by this route (3 hrs: p less than 0.01; 4 hrs: p less than 0.02). Prior to three hours no statistically significant difference was noted. In contrast, parenteral administration of atropine produced no significant effect upon the percutaneous absorption of aqueous methadone hydrochloride over a four-hour period. Atropine inhibition of absorption is likely due to cutaneous dehydration, and it may be drug-specific and/or dose-related. These findings are correlated with the previously reported ethanol inhibition of percutaneous absorption. The therapeutic implications of these observations are discussed.
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The effect of parenterally administered ethanol on the percutaneous absorption of phencyclidine hydrochloride was investigated using the intact hairless (SKH, hr-1/hr-1) mouse as a model. Four hours after topical application of phencyclidine hydrochloride, the mean phencyclidine concentration (129.2 ng/g) in excised liver was significantly lower in mice that had received ethanol by intraperitoneal injection than in mice injected intraperitoneally with water (1730.1 ng/g) (p less than 0.01). When phencyclidine hydrochloride was administered by intraperitoneal injection there was no statistically significant difference between the mean concentration in liver (3442.5 ng/g) for ethanol-treated mice and that (3030.3 ng/g) for the control mice (p greater than 0.10), indicating that the observed difference was not due to enhancement of phencyclidine metabolism by ethanol. These findings suggest that ethanol inhibits the percutaneous absorption of phencyclidine hydrochloride.
Blood concentrations and clinical findings in 25 cases of overdose involving chlordiazepoxide (CDZ) alone ("pure") were compared with those in 23 cases of overdose involving ethanol in addition to CDZ ("mixed"). Both groups consisted predominantly of men who were chronic alcoholics. The mean blood CDZ concentrations did not show statistically significant difference between the two groups ("pure," 5 mg/L; "mixed," 6 mg/L). Following "pure" ingestion, patients were usually alert, and the level of consciousness showed no statistically significant correlation with the blood CDZ concentration. In contrast, after "mixed" ingestion patients were usually lethargic, and the level of consciousness correlated significantly with the blood CDZ concentration (P less than 0.05) but not with the blood ethanol concentration. In neither group was coma noted. For both groups the most common physical findings were tachycardia and dysarthria. Nystagmus was much more common following "mixed" ingestion while seizures, hyperreflexia, and hypertension were more frequent after CDZ overdose alone. Most patients were seen only in the emergency room and were discharged. The implications of these findings are discussed.
The efficacy of performing a comprehensive toxicology screen whenever ethanol is found was evaluated in 289 consecutive emergency-room cases. Males predominated in both the "pure" (ethanol only) and the "mixed" (ethanol plus other drugs) groups. The mean ethanol concentration was significantly higher for pure cases than for mixed cases (P less than 0.01). For half of the 289 cases comprehensive screening demonstrated at least one to four other drugs per case in addition to ethanol. Barbiturates, narcotic analgesics, and stimulants in that order were the most frequently found classes of drugs. The age range 21 to 40 years accounted for most of the mixed ingestions, and ethanol concentrations less than 0.20% were more commonly associated with other drugs than were those above 0.20%. Whenever ethanol is found, comprehensive toxicology screening may yield important additional information.
We evaluated blood concentrations of three nonbarbiturate sedative-hypnotics in 19 nonfatal (NF) and five fatal (F) intoxications which were "pure" (i.e. which involved only one drug each): glutethimide, 4 (NF), 3 (F); meprobamate, 9 (NF), 1 (F); and methyprylon, 6 (NF), 1 (F). For each of the 24 cases, both a comprehensive toxicology panel (including blood and urine) and the clinical history established that only a single drug had been ingested. Blood drug concentrations showed statistically significant correlation with the level of consciousness for nonfatal meprobamate intoxication (p less than 0.01) and nonfatal methyprylon intoxication (p less than 0.05). Blood glutethimide concentrations did not show such correlation. Death was associated with a mean blood glutethimide concentration in excess of 4.0 mg/dL, a blood meprobamate concentration of 20.5 mg/dL, and a blood methyprylon concentration of 11.7 mg/dL. Interpretation of blood concentrations of these compounds is discussed, and physical findings and demographic data are presented.
We evaluated blood concentrations and clinical findings in 17 cases of isopropanol (IPROH) ingestion seen over a 8.5 year period at our institution. Eight ingestions involved IPROH alone ("pure") while the remainder involved at least ethanol in addition to IPROH ("mixed"). Fourteen patients had a history of alcoholism. Admission blood IPROH concentrations ranged from 5 to 70 mg/dL while the concentration of the acetone metabolite ranged from nondetectable to 220 mg/dL. The mean acetone concentration was significantly higher for "pure" ingestions than for "mixed" ingestions (p less than 0.05); however, the mean IPROH concentrations showed no significant difference. The mean anion gap was significantly higher for "mixed" ingestions than for "pure" ones (p less than 0.01). Fifteen patients were either alert or lethargic while two, who had ingested no compounds other than IPROH, were comatose. The most common other physical findings were tachycardia (10 cases), decreased deep tendon reflexes (5), dysarthria (4), and ataxia, hypotension, fever, and mydriasis (3 cases each). None of the findings including level of consciousness showed statistically significant correlation with the IPROH concentrations. Twelve patients were hospitalized; eleven of these recovered with supportive care alone. One patient expired from trauma suffered in a motor vehicle accident.
We report a thin-layer-chromatographic micro-analysis for quinidine in serum, with detection by fluorescence densitometry. Quinidine is extracted from 20 microL of serum at pH 13 into 3 mL of hexane/acetone solution (80/20 by vol) containing N-(1-naphthyl)ethylenediamine as internal standard. The extract is concentrated and applied to silica-gel-impregnated plates for conventional thin-layer chromatography. Quinidine is identified from its RF value and quantified from the peak-height ratio between quinidine and the internal standard, relative to that of simultaneously extracted serum standards. The proposed assay is sensitive (to 0.2 mg/L), specific for unmetabolized quinidine, precise (between-run coefficients of variation less than 6%), and readily adaptable to large-scale "batch" analysis. Peak-height ratio is linearly related to concentration to at least 20 mg/L. Quinidine concentrations in the serum of patients, as measured by the proposed method (x) and by a traditional double-extraction spectrofluorometric assay (y), were related as follows: y = 0.994x + 0.276 (r = 0.989, n = 20).
We describe a reversed-phase liquid-chromatographic assay suitable for therapeutic monitoring of thiopental and pentobarbital simultaneously in human serum. The drugs are extracted from serum at pH 6.6 into n-butyl chloride containing thiamylal and barbital as the respective internal standards. The compounds are back-extracted into dilute sodium hydroxide, an aliquot of which is submitted to chromatography. The lowest measurable concentrations are 1.0 mg/L for thiopental and 2.0 mg/L for pentobarbital. The standard curve is linear from 0 to 100 mg/L for both. Between-run CVs are: at 25 mg/L, 4.1% (thiopental) and 3.2% (pentobarbital); at 50 mg/L, 2.8% (thiopental) and 3.4% (pentobarbital). Data on patients receiving thiopental and pentobarbital illustrate use of the method.
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A popular colorimetric analysis for serum acetaminophen, based on ring-nitration of the drug, is demonstrated to yield both "false positives" and erroneously high results for serum from uremic patients. The interference appears to be anionic at physiological pH, and correlates significantly with serum creatine concentration and with the magnitude of the "anion gap." A modification of the analysis involving extraction of the acetaminophen with ether eliminates the interference. As little as 10 mg of drug per liter can be accurately measured in serum by the proposed procedure. Analytical recovery was 97% at a concentration of 1 g/L. Coefficients of variation for the analysis at respective concentrations of 100 and 500 mg/L were: within-run, 2.7% and 2.0%; between-run, 3.1% and 4.2%. I encountered no serious interferences from other drugs. The proposed method, rapid and reliable, is recommended for routine use in the clinical laboratory.
Fifty-seven cases of meprobamate ingestion from 1974 through 1979 were reviewed. Serum meprobamate concentrations, clinical findings, and epidemiologic data were studied to determine the present status of the abuse of this compound. The average patient was a 37-year-old woman who ingested meprobamate and at least one other drug (usually a benzodiazepine, a barbiturate, ethanol, or an opiate) in a suicide attempt of gesture. She arrived at the hospital either alert or lethargic with equal frequency. Half of the time she was seen only in the emergency room, and half of the time she was hospitalized. She was usually treated with supportive care alone and survived the ingestion. Serum meprobamate concentrations exceeding 12 mg/dl were consistent with coma. Dysarthria, hypotension, tachycardia, and ataxia were the most common physical findings. Meprobamate addiction was present in six patients.