Determination of ketamine and some in vivo metabolites using high-pressure liquid chromatography.
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Chromatography, Gas↗
Biomedical subjects
L L Needham
Publications and source records attributed to L L Needham.
Determination of ethchlorvynol by high-pressure liquid chromatography.
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Animals↗
Synthesis of thieno[2,3-b]azepin-4-ones as potential antineoplastic agents.
In view of the antitumor activity reported for 7,8-dimethylbenzo[b]azepine-2,5-dione, new isosteric thieno[2,3-b]-azepin-4-ones have been prepared by a Dieckmann ring closure reaction. Substituted 2-amino-3-carbethoxythiophenes were tosylated, or benzoylated, and the corresponding sodium salt was alkylated with ethyl 4-bromobutyrate. The resulting product was cyclized in the presence of sodium hydride, and the azepinones were detosylated with 40% sulfuric acid-acetic acid solution. Preliminary biological data do not indicate any siginificant antineoplastic activity.
Animals↗
A training program in bioanalytical toxicology.
Students of diversified backgrounds are taught methods used in bioanalytical toxicology such as TLC, GLC, RIA, EMIT, UV, and spectrofluorometry. Major emphasis is placed on the detection of abused drugs in biologic specimens. It was found that the students with more advanced formal education have learned the lecture theory and instrumentation quicker and in greater detail. However, as far as the ability to work rapidly and accurately, many of the trainees who have had less formal education have shown better ability. Perhaps it could be said that the theory is a science, whereas the work is an art. This art through practice can be better developed by some people regardless of education. On completion of this training, they will be able to help fill the great need for toxicologic technicians.
Allied Health Personnel↗
Letter: Identification of the major product from the acid-catalyzed reaction of ethchlorvynol.
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Deuterium↗
Residues of chlorinated phenols and phenoxy acid herbicides in the urine of Arkansas children.
Urine samples from 197 Arkansas children were analyzed for eight chlorinated phenols and four chlorinated phenoxy herbicides by using a new procedure that combined gas chromatography with tandem mass spectrometry. With the detection limit of 1 part per billion (ppb), six of these pesticides were detected in more than 10% of the samples. 2,5-Dichlorophenol (a metabolite of p-dichlorobenzene), and pentachlorophenol were detected in 96% and 100%, respectively, of the children's urine at median concentrations of 9 ppb and 14 ppb, respectively. 2,4,5-Trichlorophenol was detected in 54% of the children's urine at a median concentration of 1 ppb. One trichlorophenol and three other dichlorophenols were found in 3% to 27% of the samples. The herbicide 2,4-dichlorophenoxyacetic acid was observed in 20% of all samples. The concentrations of all analytes are reported as background or reference levels for use in future studies. The finding of 2,5-dichlorophenol as a ubiquitous contaminant merits further study.
2,4-Dichlorophenoxyacetic Acid↗
Pentachlorophenol measurements in body fluids of people in log homes and workplaces.
Human exposure to pentachlorophenol (PCP) was evaluated in the normal population (controls), residents of PCP-treated log homes, and persons exposed primarily in the workplace. Blood and urine samples were analyzed by gas chromatography after extraction and acetylation. For 34 controls, serum PCP values ranged from 15-75 ppb with a mean of 40 ppb. For 123 residents of log homes, serum levels ranged from 69-1,340 ppb with a mean of 420 ppb. In such homes, serum levels for children were significantly higher than those for parents, averaging 1.8 times greater. Serum and urine values for workers varied widely, depending on the workplace, with serum levels ranging from 26 to 84,900 ppb of PCP. Urinary concentrations when corrected for creatinine values correlated well (r = 0.92) with serum concentrations. Coating PCP-treated logs of home interiors with a sealant reduced serum PCP levels in the residents.
Adolescent↗
Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding.
Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4-5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p less than 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, and p,p'-DDE concentrations were corrected by total serum lipids, results from fasting and non-fasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.
Adult↗
US Army Chemical Corps Vietnam veterans health study: preliminary results.
The long-term health consequences of exposure to phenoxyherbicides used in Vietnam has been a great concern to the veterans. In addition to the Air Force Ranch Hand personnel, Army Chemical Corps personnel who served in Vietnam are thought to have had some of the highest herbicide exposures. The Department of Veterans Affairs commenced a study of veterans who served in Vietnam as members of the Army Chemical Corps and a comparison cohort of Army Chemical Corps personnel who served elsewhere. A total of 2872 Vietnam veterans and 2737 non-Vietnam veterans who served in the Army Chemical Corps were identified for inclusion in a telephone health interview survey with a random 20% sample of veterans receiving serum dioxin and other congeners assessments. In a feasibility study which included 284 Vietnam veterans and 281 non-Vietnam veterans, 100 serum assessments were conducted of which 95 were included in the analysis. Vietnam veterans with a history of spraying herbicides were found to have a statistically significant elevation in their current serum 2,3,7,8-TCDD concentrations compared to non-Vietnam veterans without a spray history (P = 0.05). Other 2,3,7,8-substituted dioxins levels were comparable to the levels found in the non-Vietnam veterans. This feasibility study demonstrated that serum dioxin concentrations from a sample of the study participants can be used to identify exposure variables in the health survey that can serve as a surrogate measure of phenoxyherbicide exposure.
Adult↗
Background levels of non-ortho-substituted (coplanar) polychlorinated biphenyls in human serum of Missouri residents.
This study characterizes the levels of polychlorinated biphenyls (PCB) congeners PCB 77, PCB 81, PCB 126, and PCB 169, in a group of 150 men and women with no documented exposure to PCBs. Its purpose is to provide current referent levels of coplanar PCBs in Missouri residents and to compare those levels to levels reported in the literature from the United States and other countries. Although this study used an extensive questionnaire assessing potential sources of exposure, no positive relations were found between these exposure sources and participants' PCB levels. The PCB levels for the four congeners measured were lower than any reported in the literature. PCBs 126 and 169 are only two of the dioxin-like congeners; however, their contribution makes up 11% of the total TEQ. Age was significantly related to PCB 126 and PCB 169. For every one-year increase in age, both PCB congeners increased by approximately 0.4 parts per trillion (ppt). There was no gender difference for PCB 126; however, PCB 169 levels were 3 ppt higher in males than females.
Adult↗
Dioxin incinerator emissions exposure study Times Beach, Missouri.
PURPOSE: To determine whether living in the vicinity of a hazardous waste incinerator that was burning material contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased TCDD and toxicity equivalencies (TEQ) in individuals living near the incinerator. METHODS: Participants were randomly chosen from an area close to the incinerator and compared to participants outside of the exposure area. TCDD and related compounds were measured in blood serum before incineration, four months after incineration started, and at the end of incineration. RESULTS: Lipid adjusted serum levels of TCDD and TEQ decreased from pre-incineration to four months after incineration, and decreased further by the end of incineration. CONCLUSION: Incineration of TCDD did not result in any measurable exposure to the population surrounding the incinerator.
Adolescent↗
Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants.
Prenatal exposure to polychlorinated biphenyls (PCBs) was examined by analysis of cord tissue from 435 children from a Faroese birth cohort. Analysis of 50 paired cord blood samples showed excellent correlation with the cord tissue concentration (r=.90). Among 17 neuropsychological outcomes determined at age 7 years, the cord PCB concentration was associated with deficits on the Boston Naming Test (without cues, two-tailed P=.09 not adjusted for mercury; with cues, P=.03), the Continuous Performance Test reaction time (P=.03), and, possibly, on long-term recall on the California Verbal Learning Test (P=.15). The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure.
Child↗
A longitudinal investigation of selected pesticide metabolites in urine.
As part of a longitudinal investigation of environmental exposures to selected chemical contaminants, concentrations of the pesticide metabolites 1-naphthol (INAP), 3,5,6-trichloro-2-pyridinol (TCPY), malathion dicarboxylic acid (MDA), and atrazine mercapturate (AM) were measured in repeated samples obtained from 80 individuals in Maryland during 1995-1996. Up to six urine samples were collected from each individual at intervals of approximately 8 weeks over a 1-year period (i.e., one sample per participant in each of six cycles). INAP (median=4.2 microg/l and 3.3 microg/g creatinine) and TCPY (median=5.3 microg/l and 4.6. microg/g creatinine) were present in over 80% of the samples, while MDA and AM were detected infrequently (6.6% and <1% of samples, respectively). Geometric mean (GM) concentrations of INAP in urine did not vary significantly among sampling cycles. In contrast, GM concentrations of TCPY were significantly greater in samples collected during the spring and summer of 1996 than in the preceding fall and winter. Repeated measurements of INAP and TCPY from the same individual over time were highly variable. The average range of INAP and TCPY concentrations from the same individual were approximately 200% and 50% greater than the respective population mean levels. Geometric mean (GM) TCPY concentrations differed significantly between Caucasian (n=42, GM=5.7 microg/g creatinine) and African-American (n=11, GM=4.0 microg/g) participants and among education levels, but were not significantly different among groups classified by gender, age, or household income. In future research, environmental measurements of the parent compounds and questionnaire data collected concurrently with the biomarker data will be used to characterize the determinants of variability in the urinary pesticide metabolite levels.
Adolescent↗
Measurement of PCBs, DDE, and hexachlorobenzene in cord blood from infants born in towns adjacent to a PCB-contaminated waste site.
There are limited data on the concentrations of common contaminants--polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethene (pp'-DDE) and hexachlorobenzene (HCB)--in umbilical cord blood. Cord blood provides the primary direct measure of prenatal exposure to these contaminants, the key determinant of PCBs' neurodevelopmental toxicities. The objective of this study was to characterize cord blood levels of PCBs, pp'-DDE, and HCB among 751 infants who were born between 1993 and 1998 to mothers residing adjacent to a PCB-contaminated harbor in New Bedford, Massachusetts, and for whom the neurodevelopmental toxicities of these compounds are being studied. We refined standard analytic methods to optimize the sensitivity and precision of trace-level PCB, p,p'-DDE, and HCB measurements in blood. Using these methods, we measured the concentrations of 51 individual PCBs, their sum (sum(PCB)), p,p'-DDE, and HCB in cord serum. With correction for background contamination, the respective mean+/-SD cord serum concentrations of sum(PCB), p,p'-DDE, and HCB were 0.54+/-0.83, 0.48+/-0.94, and 0.03+/-0.04 ng/g serum. These concentrations were generally lower than those in most of the few published studies with congener-specific measures of PCBs in cord blood. However, for less-chlorinated PCB congeners (e.g., congeners 99 and 118), study samples had concentrations comparable to those in other populations, including groups at risk for high dietary PCB exposure. Of note, the contaminated harbor sediment has a relatively high proportion of less-chlorinated PCB congeners. Thus, although the sum(PCB) in study infants was not higher than concentrations in infants studied elsewhere, the relative predominance of less-chlorinated congeners was generally consistent with the characteristics of the contaminated site.
Dichlorodiphenyl Dichloroethylene↗
HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine.
The elevated exposure of children to hormonally active dietary phytoestrogens has led to the need for rapid, sensitive, and precise assays for phytoestrogen metabolites in physiological matrices. Here we report the development of a high-performance liquid chromatography (HPLC) MS/MS method for the quantitative detection of seven phytoestrogens in human serum and urine. The method uses enzymatic deconjugation of the phytoestrogen metabolites followed by solid phase extraction (SPE) and reverse-phase HPLC. The phytoestrogens are detected using a Sciex API III heated nebulizer atmospheric pressure chemical ionization (HN-APCI) interface coupled with tandem mass spectrometry. This method allows the detection of the primary dietary phytoestrogens (isoflavones and lignans) in human serum and urine with limits of detection (LODs) in the low parts per billion range. The combination of tandem mass spectrometry and chromatographic separation of the analytes helps ensure the selectivity of the method. Stable isotope-labeled internal standards for all seven analytes improve the precision of the assay, resulting in interday CV values of < 10% for most compounds studied. The accuracy and precision of the method were monitored over time using quality control (QC) samples containing known amounts of phytoestrogens. The majority of phytoestrogens in human sera and urine are present as their glucuronide and sulfate conjugates. Therefore, the thoroughness of deconjugation for each sample was monitored by the addition of a conjugated internal standard and subsequent detection of deconjugated compound. This method proves to be efficacious for measuring baseline urinary phytoestrogen levels in the American population and should prove useful for assessing the modulatory effects of dietary phytoestrogens on endocrine disrupter action in children.
Chromatography, High Pressure Liquid↗
Quantification of selected pesticide metabolites in human urine using isotope dilution high-performance liquid chromatography/tandem mass spectrometry.
The annual domestic use of pesticides is continually increasing, virtually ensuring that everyone is exposed to some level of pesticides on a regular basis through diet or environment. The potential developmental and physical adverse effects these chronic pesticide exposures have on children are of increasing concern. To adequately evaluate the potential adverse effects resulting from these exposures, accurate methods to measure the amount of the pesticide absorbed by the body must be developed. We have developed a sensitive method to measure the urinary metabolites of atrazine, diazinon, malathion, 2,4-dichlorophenoxyacetic acid (2,4-D), and certain synthetic pyrethroids in human urine. In our method, stable isotopically labeled analogues of the metabolites were spiked into the urine, which was subsequently extracted at both a neutral and acidic pH using organic solvents. The extracts were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) using atmospheric pressure chemical ionization. Our method has limits of detection ranging from 20 to 500 ng/l (parts per trillion) and relative standard deviations of less than 11%. This method has been used to measure the internal doses of these pesticides in both adults and children (n = 130) with no documented exposure to the pesticides. We detected atrazine and synthetic pyrethroid metabolites in less than 12% of the samples analyzed. The metabolites of 2,4-D, malathion, and diazinon were detected in 22%, 32%, and 57% of the samples, respectively.
Adult↗
Measurements for assessing environmental exposures to children using small amounts of serum and urine: state-of-the-art.
This paper addresses the recent advances in gas chromatographic (GC)-based instrumentation for the analytical determination of environmental toxicants using small samples. One-dimensional GC/time-of-flight mass spectrometry (TOFMS) and comprehensive two-dimensional GC (GCxGC) are shown to drastically improve sample component resolution, sensitivity and overall analytical throughput. A presentation of the concepts behind the new state-of-the-art, and results highlighting the advantages of the emerging technologies are presented.
Child↗
Utilization of umbilical cords to assess in utero exposure to persistent pesticides and polychlorinated biphenyls.
In support of a study to relate developmental and cognitive effects with prenatal exposure to selected environmental toxicants, we developed and applied an analytical method to determine the concentration of two persistent pesticides, hexachlorobenzene (HCB) and p,p'-dichlorodiphenyldichloroethylene (DDE), and 32 specific polychlorinated biphenyl (PCB) congeners in 316 umbilical cords taken in 1986-1987 from women of the Faroe Islands. The analytical method consisted of homogenization of the cords, partitioning, microsilica gel column chromatography for clean-up, and dual-column capillary gas chromatography (DB-5 and DB-1701) with electron capture detection. Several quality control parameters were followed to monitor the performance of the method. Important criteria used before reporting unknown data were the recovery of in vitro-spiked analytes from a bovine umbilical cord (BUC) and the percentage lipid obtained for a Certified Reference Material (CRM)-350 of mackerel oil (MO). Recoveries of analytes that had been spiked at two concentration ranges (0.26-0.95 ng/g whole weight; 0.35-2.42 ng/g whole weight) into bovine cords ranged from 38.5% to 158% and from 50.4% to 145%, respectively, with a median recovery of 77.7%. Measurement of the percentage lipid for CRM-350 ranged from 73.8% to 107% with a median lipid value of 96.0%. The most prevalent analytes detected (%) in unknown umbilical cords were HCB (100), DDE (100), Ballschmiter/Zell PCBs 153 (100), 138 (98), 180 (98), 170 (93), 118 (88), 187 (86), and 146 (83), with corresponding median concentrations (ng/g whole weight) of 0.17, 1.19, 0.38, 0.30, 0.17, 0.11, 0.12, 0.09, and 0.07, respectively. Total PCB--sum of all measurable PCB congeners--had a median concentration of 1.37 ng/g whole weight. The analytes, which were very low in lipid content were also quantified on a lipid-adjusted basis, which provided an analytical challenge in these umbilical cord samples. The gravimetrically measured lipids in the human specimens ranged from 0.01% to 1.43% (median of 0.18%). In the pooled BUCs, our lipid measurements varied from 0.05% to 0.33% with a median value of 0.13%. The utility of using the umbilical cord as a matrix to assess in utero exposure to persistent environmental pollutants, compared with the use of umbilical cord blood or mother's blood, is worthy of debate.
Adult↗