Showing papers in "Journal of Analytical Toxicology in 1977"
TL;DR: Although the relationship between toxicity and hair arsenic concentration was rather varied, 1 ppm appears to be satisfactory upper limit of acceptability for drinking water, but leave little safety margin.
Abstract: In this study of 92 people using wells with arsenic concentrations of >0.05 ppm (and with 21 control subjects), 27 of them had clinical features possibly attributable to chronic arsenic poisoning. There was a positive relationship between frequency of clinical features, and well and hair arsenic concentrations. Although the relationship between toxicity and hair arsenic concentration was rather varied, 1 ppm appears to be satisfactory upper limit of acceptability. For drinking water, an acceptable limit of 0.01 ppm and a maximum permissible limit of 0.05 ppm of arsenic appear satisfactory, but leave little safety margin.
85 citations
TL;DR: Data on the concentrations in human blood, plasma or serum of drugs of interest to analytical toxicologists is compiled and refers to N-desalkyl metabolites as nor-compounds for the sake of brevity.
Abstract: We have compiled data on the concentrations in human blood, plasma or serum of drugs of interest to analytical toxicologists. The entries for each drug are representative of the available information in the literature and include other pharmacological factors necessary to the proper utilization of the data. Many of the drugs studied yield active metabolitas iN VlVO and these concentrations have also been noted where applicable. In the two years since the original version of this paper appeared (1) a wealth of information has been published relating to concentrations of therapeutic agents in humans. Many of these studies are the result of the current requirements for bioavailability and pharmacokinetic data on the newer drugs, while others can be traced to the demand for therapeutic drug monitoring and clinical toxicology services and the development of newer, more sensitive analytical techniques. In view of the ever-increasing need to have this information catalogued in a single convenient source we felt it would not be presumptuous to prepare an updated version of the information on toxicologically significant drugs at this time. An additional 60 therapeutic entries and 42 toxic entries are included in this latest compendium. All of the previous statements (1) regarding the dangers inherent in the interpretation of drug concentrations hold true. It should again be noted that these entries represent situations in which the listed drug was the only significant contributor to pharmacological effects. We have taken the liberty of referring to N-desalkyl metabolites as nor-compounds for the sake of brevity, but only in those instances in which structural clarity is not lost. Finally, included in the tables are only those drug metabolites which are known or believed to be pharmacologically active and which may contribute significantly to the overall drug effect.
72 citations
TL;DR: In this paper, a cold vapor atomic absorption method was used to determine the total and organic mercury content of whole blood, hair, urine, tissue, fish, and sediment samples.
Abstract: Total mercury was determined by the introduction of CdCl/sub 2/ in the presence of SnCl/sub 2/ to break the mercury to carbon bond with subsequent reduction of Hg/sup 2 +/ to Hg/sup 0/ which is determined by a flameless atomic absorption method. Inorganic mercury is determined in the absence of CdCl/sub 2/, and the organic mercury is calculated by the difference between total and inorganic mercury. The preparation of samples of whole blood, hair, urine, tissue, fish, and sediment samples is described in detail. Results obtained by this cold vapor atomic absorption method are shown to be in good agreement with results obtained for mercury content of samples analyzed by gas chromatography, proton microprobe, and x-ray fluorescence.
40 citations
TL;DR: Twelve subjects who transferred from methadone administered every 24 hr to I- ~ -acetylmethadol (LAAM) administered every 48 hr experienced overdosing symptoms during the study, and their plasma levels were significantly higher than those found In the other subjects.
Abstract: Methods Plasma drug concentrations were determined and behavioral observations were made in 11 subjects who transferred from methadone administered every 24 hr to I- ~ -acetylmethadol (LAAM) administered every 48 hr Plasma concentrations of methadone, LAAM and its metabolltes, noracetylmethado| [N-LAAM] and dinoracetylmethadol [DN-LAAM] were determined 24 hr after the last dose of methadone and 48 hr after each dose of LAAM for the first 10 LAAM doses (19 days). Methadone could be detected in plasma for up to 5 days after the last dose. LAAM plasma levels were low [approximately 35 ng/ml] and did not accumulate with chronic administration. Plasma levels of N-LAAM and DN-LAAM increased 3- and 4-fold respectively with time and did not reach steady state until after day 11 (dose 6). Two of the 11 subjects experienced overdosing symptoms during the study, and their plasma levels of N-LAAM and DN-LAAM were significantly higher than those found In the other subjects.
35 citations
TL;DR: In this paper, the toxicity and pharmacokinetics of chlordecone (CD) in chemical workers poisoned with this organochlorine pesticide Ingredient were investigated and a reliable and practical assay procedure for CD applicable to a variety of biological speclmens.
Abstract: We have investigated the toxicity and pharmacoklnetlcs of chlordecone (CD) In chemical workers poisoned with this organochlorine pesticide Ingredient. To achieve this objective we have developed a reliable and practical assay procedure for CD applicable to a variety of biological speclmens. A gas chromatographic method using an electron capture detector is presented together with s discussion of some of the analytical problems associated with this compound.
34 citations
TL;DR: In this paper, sensitive methods for the gas chromatographic determination of hydrogen cyanide end cyanogen in cigarette and cigar smoke are described, based upon the conversion of cyanide to cyanogen chloride by chloramine-T.
Abstract: Sensitive methods for the gas chromatographic determination of hydrogen cyanide end cyanogen In cigarette and cigar smoke are described. The HCN method Is based upon the conversion of cyanide to cyanogen chloride by chloramine-T. Cyanogen chloride, dissolved in n-hexane, Is analyzed by gas chromatography using an electron capture detector. Particulate matter and gas phase are analyzed separately. The relative standard deviation Is less than 5% (total HCN) In the smoke of a commercial cigarette with HCN concentration above 50 F g/cigarette. The mainstream smoke of the standard cigarette (85 mm, without filter tip) contains 479 /t g hydrogen cyanide whereas in mainstream smoke of plain cigarettes, filter cigarettes, litfie cigars, cigars and a marijuana cigarette HCN values range from 279 to 551 F g- Sidestream smoke of filter and nonfllter cigarettes and little cigars contains between 87 and 134 /~ g HCN; a marijuana cigarette yielded 191 Fg HCN In the sidestream. For the cyanogen determination the cigarettes and little cigars are smoked through a glass fiber filter and the gas phase is analyzed by GLC using dual gas sampling loops. The smoke of the cigarettes and little cigars fasted contains between 12 and 20Fg of (CN)2. These amounts contribute only Insignificantly to the HCN yields obtained by the above method. In the case of cigars (nonporous wrapper), we found that between 9 end 26% of the determined HCN was derived from the cyanogen in the smoke.
30 citations
TL;DR: The P/N ratio in brain was consistently the highest value when compared to blood, liver and kidney, and blood propoxyphene concentrations exceeding 0.1 mg/dl appear significant in elucidating the cause of death in the absence of other evidence.
Abstract: Propoxyphene (P) and its major metabolite, norpropoxyphene (N), have been determined in an increasing number of acute and drug abuse related medical examiner cases in Maryland during 1974-1976. Acute fatalities were typified by a female in her 30's with a P/N ratio in blood of 4.1, while drug abuse related fatalities were exemplified by a male in his 20's with a P/N ratio in blood of 1.9. Propoxyphene related fatalities were generally accompanied by the simultaneous detection of ethanol or other drugs. Blood propoxyphene concentrations exceeding 0.1 mg/dl appear significant in elucidating the cause of death in the absence of other evidence, while concentrations exceeding 0.2 mg/dl may reasonably be considered an independent causative factor in a fatality. The P/N ratio in brain was consistently the highest value when compared to blood, liver and kidney. Propoxyphene and norpropoxyphene blood and tissue concentrations and P/N ratios are useful in the diagnosis of propoxyphene related deaths.
29 citations
TL;DR: Radioimmunoassay was significantly the most sensitive method for both cocaine and benzoylecgonlne and the most efficient for the analysis moderate to large numbers of specimens.
Abstract: Four analytical techniques, chromatographic and Immunologic, were evaluated for their ability to detect cocaine end Its metabollte benzoylecgonlno In human urine. Each of the methods had advantages end limitations end was suited for specific laboratory requirements. The study showed that gas-liquid chromatography was the most precise method; thin-layer chromatography, the most applicable for determining a number of drugs simultaneously; and enzyme Immunoassay, the method with the best turn-around time for analyzing small numbers of specimens. Radioimmunoassay was significantly the most sensitive method for both cocaine and benzoylecgonlne and the most efficient for the analysis moderate to large numbers of specimens. Comprehensive evaluation studies were performed with a redioimmunoassay technique that has only recently been made available.
29 citations
TL;DR: A method for the rapid qualitative and quantitative determination of five major benzodlazepine drugs in one milliliter of human plasma is described in this paper, where the drugs are analyzed as the underivatized compounds by electron capture gas chromategraphy on a 1 meter 3% OV-17 column.
Abstract: A method for the rapid qualitative and quantitative determination of five major benzodlazepine drugs In one milliliter of human plasma is described. These drugs are analyzed as the underivatized compounds by electron capture gas chromategraphy on a 1 meter 3% OV-17 column. By virtue of the addition of N-methyl clonazepam to the plasma prior to extraction, quantitative evaluations can be made for the individual drugs from previously prepared standard curves. The data given includes the recovery responses for the Internal standard, the various drugs and their metabolites after extraction and gas chromatographic analysis. Chromatograms are illustrated for patients who had Ingested the various drugs.
27 citations
TL;DR: In this paper, a method for the determination of paraquat In plasma which involves a protein precipitation using trichloroecetlc acid, followed by a reduction of the herbicide to ether extractable compounds and subsequent gas chromatographic quantitation is described.
Abstract: A method for the determination of paraquat In plasma which involves a protein precipitation using trichloroecetlc acid, followed by a reduction of the herbicide to ether extractable compounds and subsequent gas chromatographic quantitation is described. Ethyl viologen used as an internal standard has been demonstrated to behave similarly to paraquat during the entire course of sample preparation prior to gas chromatography. Paraquat levels as low as 0.030 mg per liter can be assayed.
24 citations
TL;DR: In this article, an improved and very sensitive wet dlgestlon/extrectlon method with quantltetlon by automated electrothermal atomic absorption spectrometry (AAS) was elaborated.
Abstract: As a contribution to the evaluation of a reference method for the determination of nickel In urine and serum, systematic Investigations on the most Important analytical steps were performed. At first, by means of NI-63 as a tracer, an intercemparlaon study of dry end wet ashlng was made. The latter was found to be superior. Thus, an Improved and very sensitive wet dlgestlon/extrectlon method with quantltetlon by automated electrothermal atomic absorption spectrometry (AAS) was elaborated. Furthermore, using N1-63 as before, the extraction efflclencles for the chelating agents ammonium pyrrolldlne dlthlocerbemate (APDC), furlldloxlme (FD), and dimethylglyoxlme (DMG), end the solvent methylisobutylketone (MIBK) were determined. Under standardized conditions APDC showed the highest efficiency (> 99%) end repeatability. In an lntercomperlson test of the average peak height of the nickel chelates studied by electrothermal AAS, rather high responses for NI-FD compared with the other compounds were obtained. Further, the performance of the chosen method, Its sensitivity, and low-blank level (> 0.5 p.g/I) ere demonstrated, end data on Intercomparison measurements In spiked and unaplked solutions ere presented. Average nickel values In the urine from occupationally unexposed persons expressed as Fg / 1 (n = 37) or Fg/24 h (n = 16) are 2.04 1.0 and 1.7 ~ 1.5, respectively. Finally, the results of these Investigations from the view of the present state-of-art of uitratrece analysis and the precticel requirements for quality control and supervision are crltlcelly discussed.
TL;DR: In this article, a method for the routine determination for toxicological purposes of the common benzodlazepines In biological fluids and tissues was presented for the purpose of identifying and quantifying at concentrations of 0.2 ug/ml or greater.
Abstract: A method is presented for the routine determination for toxicological purposes of the common benzodlazepines In biological fluids and tissues. The procedure makes use of flameionization gas-liquid chromatography without prior derlvatlzation of the drugs, and it employs prazepam as an Internal standard. Diazepam, nordlazepam, flurazepam, desalkylflurazepam, chlordiazepoxide, and oxazepam may be Identified and quantitated at concentrations of 0.2 ug/ml or greater. A thin-layer chromatographic technique has been Included for the purposes of confirming the Identity of the drugs analyzed with this procedure.
TL;DR: It is demonstrated that 88 percent of the laboratories were performing satisfactory phenytoln assays, and the performance on phenobarbital prlmldone, carbamazeplne and ethosuximide assays demonstrates a marked Improvement.
Abstract: Significant improvement In the therapeutic monitoring of antieplleptlc drug concentrations In the laboratories partlclparing In the Antleplleptlc Drug Quality Control Program has been observed. In contrast to the 1974 blind survey results where over 50 percent of the laboratories were unsatisfactory, a recent assessment of performance based upon results from monthly proficiency samples demonstrates that 88 percent of the laboratories were performing satisfactory phenytoln assays. The performance on phenobarbital prlmldone, carbamazeplne and ethosuximide assays also demonstrates a marked Improvement. Proficiency testing has significantly improved the routine of
TL;DR: Toxicological analysis revealed the following concentration of this compound, diphenhydramlne, in blood, brain, and urine; urine, 6.4 mcglml; gastric [total], 554 rag; methods for the detection and quantltatlon of the drug are described.
Abstract: A suicidal death is described Involving diphenhydramlne. Toxicological analysis revealed the following concentration of this compound: blood, 31.0 mcg/ml; brain, 32.0 mcg/g; urine, 6.4 mcglml; gastric [total], 554 rag. Methods for the detection and quantltatlon of the drug are described.
TL;DR: A colorlmetrlc method for the rapid estimation of ecetamlnophen In serum is presented and the reaction Is linear over the range found in suspected overdose.
Abstract: A colorlmetrlc method for the rapid estimation of ecetamlnophen In serum Is presented. A procedure previously designed for measuring overdose levels has been medlfled to permit quantltatlon In the therapeutic range. The reaction Is linear over the range found In suspected overdose.
TL;DR: A simple and rapid heed space mess spectrometric screening technique for volatlles in blood and post-mortem tissues is described in this paper, where the presence of the volatile anesthetic agents, nitrous oxide, halothane (Fluothane) and enflurane (Ethrane), in the blood of surgical patients is demonstrated.
Abstract: A simple and rapid heed space mess spectrometric screening technique for volatlles in blood and post-mortem tissues Is described. Mass spectral data on specimens trom acute toxicities due to fluorocarbons (Freens), methane, diethylether, and toluene are presented. The presence of the volatile anesthetic agents, nitrous oxide, halothane (Fluothane) and enflurane (Ethrane), in the blood of surgical patients is demonstrated. Xylene, toluene, CCl4, CHCl3, acetonitrlle, and methylethylketone In blood-enriched specimens also exhibit characteristic mass spectra. The detection limit for this technique Is approximately 1/~g / ml.
TL;DR: A gas chromatographic procedure is presented for routine detection and quantltatlon of methadone and its metabolltes in biological fluids and tissues in this paper, which employs an extraction of drugs with n-butyl chloride at approximately neutral pH and chromstogrephlc Identification on 3% OV-17 using SKF-525-A and n-docosane as Internal standards.
Abstract: A gas chromatographic procedure is presented for routine detection and quantltatlon of methadone and its metabolltes in biological fluids and tissues. The method employs an extraction of drugs with n-butyl chloride at approximately neutral pH and chromstogrephlc Identification on 3% OV-17 using SKF-525-A and n-docosane as Internal standards. A modified extraction apparatus and the recovery of methadone, 1,5-dimethyl-3,3-diphenyl~,ethylidene-pyrrolidine (Mbl), and SKF-525-A from s variety of fluids and tissues are described. The method is sensitive to 20 ng/ml or g and is applicable to other basic drugs.
TL;DR: In this paper, an automatic sample dispenser was used for the analysis of lead and cadmium in a nitric acid-blood mixture, with a relative standard deviation of 2-5% for lead and 3-6% for cad mium using 2-FI sample volumes.
Abstract: Furnace atomic absorption has been coupled with an automatic sample dispenser and used for the analysis of lead and cadmium in a nitric acid-blood mixture. Relative standard deviations of 2-5% for lead and 3-6% for cadmium have been measured using 2-FI sample volumes. The accuracy of the method has been established by a chelation and solvent extraction technique followed by flame AA analysis.
TL;DR: A thin-layer chromatographic method for simultaneous screening and confirmation of phencyclidine in urine specimens is presented in this article, where the organic solvent is concentrated and the residue is spotted, half on each of two thin layer chromatography plates, one plate is developed in ethyl acetate: methanol: dlethylamlne [90:10:16] solvent system and the second in methylene chloride: n-butanoh concentratod ammonium hydroxide [85:15:02] phencycUdlne In concentrations as
Abstract: Experimental A thin-layer chromatographic method for the simultaneous screening and confirmation of phencyclidine In urine specimens Is presented Urine specimens ere made basic and extracted with organic solvent The organic solvent Is concentrated and the residue spotted, half on each of two thin-layer chromatography plates One plate is developed in ethyl acetate: methanol: dlethylamlne [90:10:16] solvent system and the second In methylene chloride: n-butanoh concentratod ammonium hydroxide [85:15:02] PhencycUdlne In concentrations as low as 02 ug/ml can be detected without Interference from other drugs and urinary substances
TL;DR: It was found that the results obtained from the analysis of whole blood were comparable to the serum theophylline concentrations, and good correlation was observed between the high-pressure liquid chromatographic and spectrophotometric method.
Abstract: A high-pressure liquid chromatographic procedure for theophylline, which can be applied to both ante-mortem and post-mortem samples, is described. The procedure routinely requires a 250p.I sample but as little as 50p.I of serum can be analyzed. Analytical results obtained using the described high-pressure liquid chromatographic procedure are compared with those obtained using a spectrophotometric method. In addition, whole-blood and sera specimens collected at the same time were analyzed and the results compared. Good correlation was observed between the high-pressure liquid chromatographic and spectrophotometric method. It was also found that the results obtained from the analysis of whole blood were comparable to the serum theophylline concentrations.
TL;DR: In this paper, a tritium-labeled amitriptyline antibody was used for detection and exclusion of tricyclic antidepressant compounds in biological specimens, and the sensitivity of the assay is in 2-5 nanogram range.
Abstract: A. 7 4 8 3 Antisera to nortriptyline and desipramine were produced in ~ z ~ rabbits against their succinylated derivatives conjugated to bovine serum albumin and bovine thyroglobulin, respect- Nortriptyline: R= CH(CH2)2NHCH 3 Oesipramine:R= (CH2)3NHCH 3 ively. The antibodies thus produced were shown to be specific for tricyclic antidepressant group of drugs. Some of the Arnitriptyline:R= CH(CH2)2N{CH3) 2 Irnipramine: R= (CH2)3N(CH3) 2 phenothiazines cross-reacted in higher concentrations. The assay was useful when either antibody was combined with generally or specifically tritium-labelled amitriptyline and nortriptyline. The sensitivity of the assay is in 2-5 nanogram range and is usful in screening for use and abuse of trlcyclics by man. Comparison of RIA results with thin-layer and gas chromatography have been made, and good agreement is reported. Combined with a thin-layer and/or gas-chromato- graphic confirmation, the test is well suited for detection and exclusion of these compounds in biological specimens.
TL;DR: Urine specimens collected from patients on methadone therapy were analyzed by enzyme multiplied immunoassay technique, hemagglutinatlon inhibition, radiolmmunoassay, thin layer and gas liquid chromatography, and the results obtained by all five methods are compared.
Abstract: One hundred urine specimens collected from patients on methadone therapy were analyzed tor the presence of methadone and its primary metabolite [2-ethylidene-1,5-dimsthyl-3, 3-diphenylpyrrolidine] by enzyme multiplied immunoassay technique, hemagglutinatlon inhibition, radiolmmunoassay, thin layer and gas liquid chromatography. The results obtained by all five methods are compared. Immunoassays are recommended for determining the presence of methadone alone, GLC for obtaining quantitative results, and GLC and TLC for analysis of a variety of drugs at the same time as methadone and its primary metabolite.
TL;DR: Pathological findings were limited to pulmonary edema and congestion of the liver, spleen, and kidneys, and Monoamine oxidase activity in liver was markedly diminished from that of the control case, although the cerebral cortical activity of this enzyme did not differ significantly from the control.
Abstract: The case of a 55-year-old woman who died following the Ingestion of 300 mg of tranylcypromine and several other drugs is presented. High concentrations of tranylcypromine were found in blood, brain, liver, and urine by gas-liquid chromatography. Monoamine oxidase activity in liver was markedly diminished from that of the control case, although the cerebral cortical activity of this enzyme did not differ significantly from the control. Pathological findings were limited to pulmonary edema and congestion of the liver, spleen, and kidneys.
TL;DR: A convenient and rapid high-pressure liquid chromatographic (HPLC) procedure for the simultaneous analysis of MNP and DNP formed under in vitro and in vivo conditions is described.
Abstract: A high-pressure liquid chromatographic procedure for the simultaneous analysis of N-nitroso and N,N;dinitroso derivatives of piperazlne Is described. Its application in assaying these toxic nitrosamines formed under in vitro conditions in human saliva and in vivo conditions In rat stomach Is reported. Piperazine is a highly effective and widely used anthelmintic agent in the management of round worm (Ascaris lumbricoides) and pin worm (Oxyuris vermicularis) infections (1). Recently, piperazine was found to react with sodium nitrite under in vitro and in vivo conditions to yield N-nitroso (MNP) 1 and N,N'-dinitroso (DNP) derivatives (2-6). Both MNP and DNP were carcinogenic to mice and rats (7-11). Concurrent oral administration of piperazine and sodium nitrite to mice produced lung adenomas attributable to in vivo nitrosation of the drug (7). The recommended maximum oral dose of piperazine (as its adipate, calcium editate, citrate or tartrate salt) is 3.5g/day for 2 days for ascariasis and 2.Sg/day for 8 days for oxyuriasis. Because of this high intake of a readily nitrosatable drug, some investigators have expressed concern regarding its nitrosative toxification in the stomach, especially in the absence of proper attention to dietary intake of nitrite (4,6,7). Recently, a spectrophotometric (12) and several thin-layer (4,6) and gas chromatographic (2,5,13) methods were reported for the analysis of N-nitroso derivatives of piperazine. The present paper describes a convenient and rapid high-pressure liquid chromatographic (HPLC) procedure for the simultaneous analysis of MNP and DNP formed under in vitro and in vivo conditions.
TL;DR: A case of probable acute toxicity resulting from injection of silicone oil and the analysis of fixed tissues therein are described.
Abstract: Silicone oils (dimethylpolysiloxanes) may not be as biologically inert as has been generally accepted. When injected intravenously the toxicity is, in part, a function o! viscosity. A case of probable acute toxicity resulting from injection of silicone oil and the analysis of fixed tissues therein are described.
TL;DR: A radloimmunoassay for hydromorphone In plasma has been developed from a commercially available RIA kit and is capable of detecting drugs in the 10 - 40 ng/ml range using 0.1 ml of sample.
Abstract: A radloimmunoassay for hydromorphone In plasma has been developed from a commercially available RIA kit. The method is capable of detecting drugs in the 10 - 40 ng/ml range using 0.1 ml of sample. Accuracy of the procedure using spiked human plasma samples Is + 20%. Analysis of