Methanol intoxication: distribution in postmortem tissues and fluids including vitreous humor

A 44-year-old man was found unconscious beneath an elevated rapid transit right-of-way. On admission to the emergency room, the patient was comatose in metabolic acidosis with high anion and osmolal gaps. The serum methanol was 583 mg/dL. The serum ethanol and ethylene glycol were negative. The patient was treated with ethanol, bicarbonate, and hemodialysis. He expired 40 h after admission. The postmortem methanol concentrations in body fluids were as follows: bile 175 mg/dL, vitreous humor 173 mg/dL, and blood 142 mg/dL. Urine was not available for analysis. Postmortem methanol concentrations in body tissues are given in decreasing order: brain 159 mg/100 g, kidney 130 mg/100 g, lung 127 mg/100 g, spleen 125 mg/100 g, skeletal muscle 112 mg/100 g, pancreas 109 mg/100 g, liver 107 mg/100 g, and heart 93 mg/100 g. The total amount of methanol in the gastric contents was 73 mg. Methanol determinations were performed on a Hewlett-Packard 5840A gas chromatograph with flame ionization detection using a glass column packed with 0.2% Carbowax 1500 on Carbopack C. The internal standard used was n-propyl alcohol.     

Concentration-time profiles of ethanol in capillary blood after ingestion of beer.

Blood ethanol profiles were determined in experiments with healthy volunteers after they had drunk beer. When 330 ml of light beer (1.8% w/v ethanol) was consumed in 5 min by four men and four women, the average peak blood-alcohol concentration (BAC) reached was 8 mg/100 ml (range 2-11). After nine men had drunk 660 ml of beer (3.0% w/v or 3.6% w/v ethanol) in 25 minutes on an empty stomach, the average peak BAC was 32 mg/100 ml (range 26-44) and 37 mg/100 ml (range 23-54) respectively. When the same two beers were consumed by another nine men together with a meal, the peak BAC was 24 mg/100 ml (range 20-29) and 28 mg/100 ml (range 20-39) respectively. The peak BAC occurred earlier when beer was ingested together with food; mean 32 min (range 30-50) compared with 41 min (range 30-70) with an empty stomach. The rate of disappearance of alcohol from blood (beta-slope) was 12 mg/100 ml/h in the fed state and 15 mg/100 ml/h when subjects were fasted. The apparent volume of distribution of ethanol (Vd) was 0.65 l/kg (SD 0.07) for the empty stomach condition but exceeded unity when beer was ingested together with food. It seems that part of the dose of alcohol when consumed with food never reaches the systemic circulation.     

Report of a fatal, acute tripelennamine intoxication.

A death resulting from tripelennamine overdose in a 19-year-old male Caucasian is reported. The patient died 7 h after ingesting approximately twenty 50-mg tripelennamine tablets. A concentration of 1.0 mg/100 ml was found in the blood. All tissue concentrations were measured by ultraviolet spectroscopy and verified by gas-liquid chromatography. Significant findings included pulmonary edema and multiple small petechial hemorrhages in the soft tissue of the scalp.     

Suicidal buflomedil intoxication

A suicidal intoxication of a young woman following an overdose of buflomedil is reported. She died in a hospital 17 hours after ingestion. In various body fluids the following buflomedil concentrations were determined: heart blood 24.5 microg/ml, liquor 21.3 microg/ml, bile 39.1 mg/ml and urine 138.6 mg/ml. Additionally the results of autopsy and histology are presented. Anemia of the internal organs was conspicuous; this finding is attributed to the vasodilating effect of buflomedil on the peripheral vessels.     

Alcohol metabolism of local Chinese in Hong Kong: a statistical determination on the effects of various physiological factors

A study was designed to examine the elimination rate of alcohol from the body of the local Chinese after consumption of different types of alcoholic drinks. The breath alcohol of 184 healthy volunteers was determined and converted into blood alcohol levels after they finished drinking. Information on the type and volume of alcoholic drinks consumed, age group, sex, drinking habit, and drinking on empty stomach or with/after meal was recorded for each participant. The results show that the elimination rate of an individual can be explained in terms of physiological variables including sex and drinking habit. The determined elimination rates allow forensic toxicologists to back calculate the blood alcohol concentration (BAC) of the drivers at the time of accident in drunk driving cases. The elimination rates of blood alcohol at 95% prediction intervals for male and female are in the range of 9.5-23.8 mg/100 ml/h and 11.1-37.1 mg/100 ml/h, respectively.     

Evaluation of breath alcohol instruments II. In vivo experiments with Alcolmeter Pocket Model

The precision and accuracy of an Alcolmeter Pocket Model breath alcohol instrument have been investigated in experiments with human subjects under controlled conditions. The instrument response was zero in all tests with breath samples from alcohol-free subjects. The standard deviations of ethanol determinations in breath were ±0.0722 mg/ml during ethanol absorption and ±0.0416 mg/ml during ethanol elimination. The standard deviation during the elimination phase increased with ethanol concentration in the sample, being ±0.0416 mg/ml on average at a mean concentration of 0.420 mg/ml, corresponding to a coefficient of variation of 9.9%.The blood alcohol estimates using the Alcolmeter were somewhat too high during active absorption of ethanol, and too low during elimination, when a constant blood-breath alcohol ratio of 2100:1 was used to calibrate the instrument. During the elimination phase of ethanol kinetics and at a mean blood alcohol concentration of 0.50 mg/ml, the mean Alcolmeter result was 0.456 ± 0.169 mg/ml with 95% confidence, i.e. varying between 0.287 and 0.625 mg/ml 95 times out of 100 tests at this critical blood alcohol level.     

Fatal outcome of poisoning with ethylene glycol

After an act of violence, a delinquent swallowed about 250 ml ethylene glycol (EG) - probably to commit suicide before being arrested. During an interrogation by the police he appeared to be inebriated. A blood sample taken at this time did not contain ethanol but 5.1 g/l EG, as revealed by the analytical results. Only after a second examination was he taken to an intensive care unit in a hospital in spite of signs of pronounced intoxication after 12 h at the first examination. The patient died 30 h after taking EG without being effectively treated. The correct diagnosis, initiated by information from the poison control center, was made too late. At autopsy, findings were indicative of stage II of EG poisoning with a body burden of still 40-60 g EG. The mean rate of degradation in the blood was approximately 0.15 g/l per hour.     

Plasma,oral fluid and sweat wipe ecstasy concentrations in controlled and real life conditions

In a double-blind placebo controlled study on psychomotor skills important for car driving (Study 1), a 75 mg dose of +/- 3,4-methylenedioxymethamphetamine (MDMA) was administered orally to 12 healthy volunteers who were known to be recreational MDMA-users. Toxicokinetic data were gathered by analysis of blood, urine, oral fluid and sweat wipes collected during the first 5h after administration. Resultant plasma concentrations varied from 21 to 295 ng/ml, with an average peak concentration of 178 ng/ml observed between 2 and 4h after administration. MDA concentrations never exceeded 20 ng/ml. Corresponding MDMA concentrations in oral fluid, as measured with a specific LC-MS/MS method (which required only 50 microl of oral fluid), generally exceeded those in plasma and peaked at an average concentration of 1215 ng/ml. A substantial intra- and inter-subject variability was observed with this matrix, and values ranged from 50 to 6982 ng/ml MDMA. Somewhat surprisingly, even 4-5h after ingestion, the MDMA levels in sweat only averaged 25 ng/wipe. In addition to this controlled study, data were collected from 19 MDMA-users who participated in a driving simulator study (Study 2), comparing sober non-drug conditions with MDMA-only and multiple drug use conditions. In this particular study, urine samples were used for general drug screening and oral fluid was collected as an alternative to blood sampling. Analysis of oral fluid samples by LC-MS/MS revealed an average MDMA/MDEA concentration of 1121 ng/ml in the MDMA-only condition, with large inter-subject variability. This was also the case in the multiple drug condition, where generally, significantly higher concentrations of MDMA, MDEA and/or amphetamine were detected in the oral fluid samples. Urine screening revealed the presence of combinations such as MDMA, MDEA, amph, cannabis, cocaine, LSD and psilocine in the multiple-drug condition.     

Homicidal ethylene glycol intoxication: a report of a case

We report a case of a 75-year-old hypertensive, diabetic man who presented to the emergency room with symptoms and signs of nausea, acute intoxication, significant alteration in mental status with rapid neurologic deterioration, and blunt impact injuries sustained during a recent altercation with a 36-year-old female companion-caretaker. He denied a history of ethanol abuse or other recent toxic ingestion and had not been diagnosed with or treated for depression. Hospital laboratory tests revealed a metabolic acidosis and a negative urine toxicology screen. He was diagnosed with toxic encephalopathy with metabolic acidosis secondary to metformin. Despite treatments including hemodialysis, he expired after approximately 28 hours of hospitalization. A postmortem anatomic examination revealed recent blunt-impact injuries and cardiac and renal pathology. A subsequent histologic examination revealed the presence of calcium oxalate crystals in the kidneys and brain, in addition to cardiac and renal pathology. Comprehensive forensic toxicologic testing was performed on antemortem and postmortem samples and revealed lethal levels of ethylene glycol. The cause of death was as a result of acute intoxication by ethylene glycol with another condition of multiple blunt impacts to the head, trunk, and extremities. The manner of death was ruled as homicide. A trial by jury, involving the female companion-caretaker, resulted in her conviction, and she was sentenced to 23 years to life in prison. In this report, we present an unusual case of homicidal ethylene glycol intoxication in which legal proceedings have occurred.     

Evaluation of breath-alcohol instruments. III. Controlled field trial with Alcolmeter pocket model

A breath-alcohol screening device, Alcolmeter pocket model, was evaluated in a controlled field trial with policeman operating the instruments. The results of tests made with subjects before they drank alcohol were always zero. The standard deviation (S.D.) of breath alcohol determinations increased with increase in the concentration of alcohol in the sample, being 0.036 mg/ml at a mean blood-ethanol concentration of 0.53 mg/ml. The S.D. varied among subjects tested (from 0.022 to 0.053 mg/ml) as well as among the instruments used (from 0.023 to 0.054 mg/ml). The breath test results were on average less than the actual blood-ethanol concentrations when a 2100: 1 blood/breath ratio was used to calibrate the Alcolmeter device. Blood ethanol (x) and Alcolmeter readings (y) were highly correlated (r = 0.95 +/- 0.018) and the regression equation was y = -0.017 + 0.95x. At a mean blood-ethanol concentration of 0.50 mg/ml, the Alcolmeter instrument will indicate 0.46 mg/ml on average. The standard error estimate was 0.085 mg/ml, being 17% of the mean Alcolmeter reading and this corresponds to 95% confidence limits of +/- 0.17 mg/ml. The results of this study show that Alcolmeter pocket-model is a useful device for breath-alcohol screening purposes at a blood-alcohol level of 0.50 mg/ml. A blood/breath ratio of 2300 should be used to calibrate the Alcolmeter device.     

The determination of ethylene glycol in blood and urine

Method of ethylene glycol isolation from blood and urine with subsequent gas-chromatographic determination was developed. The method makes it possible to extract 60-80% of ethylene glycol and to detect its toxic concentration in the cadaveric blood and urine.     

Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values

Four multi-elementary metal and metalloid quantification methods using inductively coupled plasma mass spectrometry (ICP-MS) were developed and validated in human whole blood, plasma, urine and hair by means of a single preparation procedure for each sample. The ICP-MS measurements were performed using a Thermo Elemental X7CCT series and PlasmaLab software without a dynamic reaction cell. With this procedure 27-32 elements can be simultaneously quantified in biological matrices: Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, Pb, Bi, U. Whole blood, plasma and urine samples (0.4 ml each) were diluted with purified water, acid, triton X100 and butanol. Rhodium was used as internal standard. The urine sample results were corrected for enzymatic creatinine determination. Twenty-five milligrams hair samples were acid mineralized after a decontamination procedure and diluted as previously described for biological fluids. To be validated, each element had to show linearity with a correlation coefficient higher than 0.99. The intra-assay and inter-assay inaccuracy, measured as the variation coefficient, were below 5 and 10% respectively. Global performance was assessed by a quality control program. Our laboratory is a registered participant of the Institut National de Santé Publique du Québec (Sainte-Foy, Canada) inter-laboratory comparison program for whole blood, urine, and beard hair of non-occupationally exposed individuals spiked with selected elements. In our study multi-element metal and metalloid analysis was assessed for 27 elements in whole blood, 27 elements in plasma, 30 elements in urine and 32 elements in hair, from 0 to 25, or 250 to 1000 ng/ml, depending on the element. Quantification limits ranged from 0.002 ng/ml (U) to 8.1 ng/ml (Al) for whole blood, from 0.002 ng/ml (U) to 7.7 ng/ml (Al) for plasma, from 0.001 ng/ml (U) to 2.2 ng/ml (Se) for urine, and from 0.2 pg/mg (Tl) to 0.5 ng/mg (B) for hair. Normal values were determined in whole blood (n=100), plasma (n=100), urine (n=100), and hair (n=45) of healthy volunteers, leading to approximately 10,000 analyses. All results are presented and discussed. Clinical toxicology and forensic toxicology applications are also reported. ICP-MS has made significant advances in the field of clinical biology, particularly in toxicological analysis. This is due to the use of extremely effective equipment that permits better clinical and forensic toxicological analysis of metal and metalloid status of each individual patient.     

运用神经行为测试系统评价酒后行为功能的可行性研究

目的研究运用神经行为测试系统评价酒后行为功能的可行性。方法采用汉化第三版计算机化神经行为评价系统(NES-C3),通过自身对照的方式,对49名饮酒者进行神经行为功能的测试,并与步行回转试验进行比较。结果心算、视觉保留、线条判断和数字筛选均在酒后0.5￣2.5h的时间点上能力指数有所下降,视简单反应时能力指数下降则延续至酒后5.5h;步行回转在酒后0.5￣2.5h间有阳性案例。血中酒精质量浓度在0.50mg/mL以上,视觉保留、线条判断及视简单反应时的能力指数有明显下降;血中酒精质量浓度在0.80mg/mL以上,心算和数字筛选的能力指数有明显下降。步行回转实验的阳性人数在血中酒精质量浓度0.50mg/mL以上有明显增加。结论计算机化神经行为评价系统作为一个定量指标,可反应酒精质量浓度与神经行为功能的关系,且比步行回转试验更客观、更灵敏。     

固相微萃取-气相色谱质谱法测定血浆中的氯氮平浓度

目的建立固相微萃取-气相色谱质谱法测定人血浆中氯氮平浓度的方法。方法以固相微萃取法提取血浆中的氯氮平,萃取头为100μm聚二甲基硅氧烷,洛沙平作内标,用气相色谱质谱选择离子法进行检测。结果本文建立的方法在5~2000 ng/ml浓度范围内呈线性关系,检测限为0.1 ng/ml(信噪比>3),低、中、高浓度(100、500、1000 ng/ml)平均相对回收率分别为98.6%、94.6%和94.6%,日内、日间RSD分别小于7.4%和7.1%。结论本文建立的固相微萃取-气相色谱质谱法灵敏度高、准确度好、操作简便,适用于氯氮平急性中毒案件的检测。     

Comparative measurement of cocaine and its metabolites in blood, cerebrospinal fluid and the brain

This study investigated the transfer of cocaine and its metabolites from plasma into the cerebrospinal fluid. The concentration of cocaine and its metabolites in plasma and cerebrospinal fluid was determined by radioimmunoassay because this method only, the sum of the drug and metabolites restored. In sheeps a sublethal cocaine hydrochloride dose (2,4 mg/kg b. wt.) was administered intraarterial daily for up to 8 days. In the first hours after administration the concentration of cocaine in cerebrospinal fluid was low. It is supposed that a barrier against the transport of cocaine from blood into cerebrospinal fluid exists. After intrathecal administration a delay of transport could from CSF to blood not be seen.     

生物组织检材内异烟肼的薄层色谱扫描检测研究──附1例异烟肼中毒死亡者体内分布报告

改进血清中异烟肼的提取方法，建立了生物组织检材内异胭肼的提取和薄层色谱扫描检测方法，线性范围为2～32ug／ml或g，检出限为0．5ug／ml或g。l例异烟擀中毒死亡者体内异烟肼分布：肾31．6mg／100g、肝26．6mg／100g、脾22．1mg／100g、心21．3mg／100g、胃16．6mg／100g、脑15．5mg／100m、肺12．6mm／100g、小脑11．7mm／100g和10.5mm／100ml。     

Plasma versus bone marrow flurazepam concentration in rabbits

Methods for the quantitation of flurazepam in plasma and bone marrow were developed for the purpose of determining the relationship between flurazepam concentrations in both tissues.Albino New Zealand rabbits, given flurazepam in doses of 5, 10, or 20 mg/kg, were sacrificed either one or three hours after drug administration. Flurazepam concentrations in plasma and bone marrow were determined utilizing a gas-liquid chromatograph equipped with an electron capture detector. The average plasma/bone marrow flurazepam ratios were 0.033 ± 0.012 and 0.024 ± 0.012 for rabbits sacrificed one hour and three hours after dosing, respectively. This study showed that a range of plasma flurazepam levels can be estimated from known bone marrow concentrations. The overall mean plasma/bone marrow ratio for all rabbits used in this study was 0.029 ± 0.012 with a range of 0.010 to 0.055.     

Evaluation of breath alcohol instruments I. In vitro experiments with Alcolmeter Pocket Model

An Alcolmeter Pocket Model breath alcohol device, based on an electrochemical (fuel cell) oxidation principle for ethanol analysis, has been evaluated under in vitro conditions. The result of a test is displayed on an analogue meter within 20 – 30 seconds after sampling; replicate tests may be made within 3 – 5 minutes. The electrochemical detector used was found to respond to acetaldehyde, methanol, isopropanol and n-propanol vapours besides ethanol, but it was insensitive to acetone vapour. The Alcolmeter response with a 0 – 2.0 mg/ml scale was linearly related to ethanol vapour concentration up to 1.0 mg/ml blood alcohol equivalent concentration; above this level the response was curvilinear, the Alcolmeter reading being too low. The standard deviation of an ethanol vapour determination in vitro was ±0.0175 mg/ml at a mean concentration of 0.902 mg/ml. The accuracy of the device expressed as percent recovery at 0.50, 1.0 and 1.4 mg/ml blood alcohol concentrations was 96.8%, 98.3%, and 88.3%, respectively. When the Alcolmeter was calibrated at 0.50 mg/ml and used occasionally each day over an 18-day period, the drop in initial calibration was 0.01 mg/ml per week.     

Distribution profile of 2,5-dimethoxy-4-bromoamphetamine (DOB) in rats after oral and subcutaneous doses

2,5-Dimethoxy-4-bromoamphetamine (DOB) is one of the potent hallucinogenic phenylalkylamines, whose ingestion has already caused several deaths reported all over the world. However, there is unsufficient information on DOB properties based on controlled pharmacokinetic studies available. The aim of this study was to clarify the distribution profile of DOB and its phenolic metabolite 2-methoxy-5-hydroxy-4-bromoamphetamine (2M5H4BA) in blood and biological tissues of experimental rats. The rats were administered a 20 mg/kg dose of DOB·HCl by oral ingestion or subcutaneous injection. Plasma and brain, liver and lung tissues were collected at 0.5, 1, 2, 4, 8, 16, and 32 h after dosing (three animals per time point). The samples were prepared by a liquid–liquid extraction procedure and the extracts were assayed by GC–MS. After per oral application, DOB peak plasma level of 320 ng/mL was reached after one-hour post dosing as well as 2M5H4BA peak concentration of 203 ng/mL. A rapid phase of DOB absorption, 2M5H4BA formation and their tissue distribution during the first two hours after application were followed by a slow decrease rate of the elimination process until 32 h. After subcutaneous application, high plasma levels of the unchanged parent drug and relatively reduced formation of its metabolite 2M5H4BA were observed. DOB maximum plasma concentration of 1143 ng/mL was reached after one-hour post application, whereas its metabolite peak level after 8 h was 213 ng/mL. The concentration profiles of both compounds in plasma after per oral and subcutaneous administration revealed the existence of significant first pass effect after per oral administration that significantly affected DOB bioavailability. DOB tissue concentrations exceeded plasma and the highest values were found in the lungs, where drug accumulation occurred with prolonged retention till 32 h after subcutaneous dose. Although the plasma/tissue transfer was more effective for the lipophilic parent drug than for its hydroxylated metabolite 2M5H4BA, the metabolite tissue levels were significant. The hallucinogenic potential of 2M5H4BA appearing in brain remains unclear as nothing is known about its pharmacological activity at present.     

Micellar electrokinetic chromatographic screening method for common sexual assault drugs administered in beverages

Recently, much attention has been given to benzodiazepines and gamma-hydroxybutyric acid (GHB) related compounds owing to their alleged widespread use as date-rape drugs. Toxicologists would greatly benefit from a screening method that allows for the simultaneous detection of both groups of substances. A new capillary electrophoresis (CE) method has been developed in the micellar mode to accomplish this separation in under 16 min using a sodium dodecyl sulfate (SDS)/sodium tetraborate/boric acid buffer with an acetonitrile organic modifier. Optimization of SDS and organic modifier concentration, along with pH, were performed on a set of standards containing eight benzodiazepines, GHB, gamma-butyrolactone, and the internal standard, sulfanilic acid. The method was shown to have a detection limit of less than 2 microg/ml for five out of eight benzodiazepines with a linear range of 2.5-100 microg/ml. The detection limit for GHB was 32 mg/ml with a linear range to 2500 microg/ml. This method was applied to the rapid analysis of spiked beverages. GHB spiked beverages were monitored after using a series of simple dilutions to determine the effects of time on the drug analysis. Possible interfering peaks from drugs of abuse and artifacts from a variety of different drink combinations were also studied in detail. A one-step liquid-liquid extraction was the only necessary sample pretreatment.