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Oberhausbergen, France

Kintz P.,X Pertise Consulting
Forensic Toxicology | Year: 2012

An injured subject receiving transfusions of blood or fluids may present with diluted samples at autopsy. Calculation of blood ethanol concentration at the time of the event can be very challenging, given potential antemortem dilution. From a complete literature survey, it seems that this topic has received little attention. The aim of this study was to investigate a case in which antemortem dilution of blood alcohol had occurred. Before death, the victim (male; 1.70 m, 70 kg) was perfused (left elbow) with a total volume of 3.25 l (1.5 l NaCl 0.9%, 1.5 l Voluven, 0.25 l sodium bicarbonate). He was pronounced dead within minutes after the perfusion. The blood alcohol concentration (right subclavian venous blood) in the autopsy sample was 0.1 g/l. The judge in charge of the case requested us to explain the influence of the perfusion in the final blood alcohol concentration, particularly because the assailant claimed that the victim was drunk, like he was. Because nonalcoholic liquid was added to the body, the subject's alcohol concentration obviously would be affected to some degree. Intravenous fluids are administered in roughly the same amounts as fluids lost by other paths, in order to maintain blood pressure. An effective approach can be the calculation of the dilution factor. Alcohol is distributed in total body water, rather than in blood. Therefore, if 3.25 l of fluid is given to a 70-kg man, with a volume of distribution of 0.70 l/kg, the total body water, and consequently the blood alcohol, is diluted by less than 10%. The premise presented for estimating the effect of dilution is mostly valid when the ethanol has reached equilibrium in the total body water (time dependent). A higher dilution of the blood alcohol concentration can occur when ethanol distribution to the total body water has not reached equilibrium. Comparisons of autopsy results with blood analysis data for hemoglobin, albumin, or total proteins collected before the incident, can be of great interest to evaluate the dilution factor. If results can be obtained within the same range, this will make allowances for the uncertainty in each calculation. Considering the relatively small amount of fluid added compared with the mean distribution volume of ethanol, the effects of antemortem intravenous fluids were thought to be minimal. The dilution factor was estimated to be in the 7-10% range. The contribution of the sampling and infusion site was considered to be minimal, given the respect by the physician for anatomical right-left separation. © 2011 Japanese Association of Forensic Toxicology and Springer.

Kintz P.,X Pertise Consulting
Therapeutic Drug Monitoring | Year: 2013

Abstract: The detection of a single drug exposure in hair (doping offence, drug-facilitated crime) is based on the presence of the compound of interest in the segment corresponding to the period of the alleged event. However, in some cases, the drug is detected in consecutive segments. As a consequence, interpretation of the results is a challenge that deserves particular attention. Literature evaluation and data obtained from the 20-year experience in drug testing in hair of the author are used as the basis to establish a theory to validate the concept of single exposure in authentic forensic cases where the drug is detected in 2 or 3 segments. The gained experience recommends to wait for 4-5 weeks after the alleged event and then to collect strands of hair. Assuming normal hair growth rate (1 cm/mo), it is advisable to cut the strand into 3 segments of 2 cm to document eventual exposure. Administration of a single dose would be confirmed by the presence of the drug in the proximal 2-cm segment (root), whereas not detected in the 2 other segments. However, in the daily experience of the author, it was noticed that sometimes (about 1 case from 10 examinations), the drug can be detected in 2 or 3 consecutive segments. Such a disposition was even observed in volunteer experiments in the literature. As it was also described for cocaine in early 1996, there is considerable variability in the area over which incorporated drug can be distributed in the hair shaft and in the rate of axial distribution of drug along the hair shaft. This can explain why a small amount of drug, as compared with the concentration in the proximal segment, can be measured in the second segment, as a result of an irregular movement. Another explanation for broadening the band of positive hair from a single dose is that drugs and metabolites are incorporated into hair during formation of the hair shaft via diffusion from sweat and other secretions. The presence of confounding interferences in the hair matrix or changes in the hair structure due to cosmetic treatments might mislead the final result of hair analysis. To qualify for a single exposure in hair, the author proposes to consider that the highest drug concentration must be detected in the segment corresponding to the period of the alleged event (calculated with a hair growth rate at 1 cm/mo) and that the measured concentration be at least 3 times higher than those measured in the previous or the following segments. This must only be done using scalp hair after cutting the hair directly close to the scalp. © 2013 by Lippincott Williams and Wilkins.

Kintz P.,X Pertise Consulting
Drug Testing and Analysis | Year: 2014

This office has been recently involved in a case dealing with child custody, where the final outcome was difficult to establish. The following concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the hair of a 21-month-old girl: 154 (0-1 cm), 198 (1-2 cm), 247 (2-3 cm), and 368 pg/mg (3-4 cm) after decontamination. Obviously, the concentrations measured in the hair were much lower than those observed in patients under daily treatment. In this sense, the frequency of exposures appears as infrequent (low level of exposure), with marked decrease in the more recent period. However, the girl was never prescribed carbamazepine and the mother, who was under carbamazepine therapy, denied any administration. The Judge asked if this could result from a single exposure and at which period. At least, three possible interpretations of the measured carbamazepine concentrations were addressed: (1) decrease in administration in the more recent period; (2) increase of body weight due to growing, so the same dosage will result in lower concentrations in hair; and (3) sweat contamination from the mother at the time the girl is with her in bed, the older hair being in contact longer with the bedding. In this case, it was impossible to conclude that the child was deliberately administered carbamazepine. The results of the analysis of hair could indicate that she was in an environment where carbamazepine was being used and where the drug was not being handled and stored with appropriate care. There are many differences between the hair from children and those from adults: hair from children is thinner and more porous, the ratio anagen and catagen phases are not maintained, and the growth rate can be different, at some periods, from the usual 1 cm/month. These differences, together with the influence of PK-PD parameters are reviewed in this paper, as a basis for suitable interpretation. In view of these results it is proposed that a single hair analysis should not be used firmly to discriminate long-term exposure to a drug when dealing with children. © 2013 John Wiley & Sons, Ltd.

Kintz P.,X Pertise Consulting
Forensic Toxicology | Year: 2012

Doxylamine is one of the first effective anti-histamine agents to have been discovered. The compound is also used as a sedative night-time cold and allergy relief drug and for its antiemetic effects. The first case involving sedation linked to the use of doxylamine as a drug-facilitated crime and subsequent impairment of a 21-year-old female victim is reported. Due to the long delay between the alleged crime and clinical examination, collection of blood or urine was of little value. Hence, the laboratory developed an original approach based on hair testing by liquid chromatography-tandem mass spectrometry. A lock of hair from the victim was collected 5 weeks after the suspected administration. After cutting into small pieces, about 20 mg of hair was incubated overnight in a phosphate buffer (pH 8.4). The aqueous phase was extracted with 5 ml of a mixture of methylene chloride/diethyl ether (80/20), in presence of haloperidol-d 4, used as internal standard (IS). The hair extract was separated on an XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Detection was based on two daughter ions: transitions m/z 271.3-182.1 and 167.0 and m/z 380.2-169.2 for doxylamine and the IS, respectively. In the hair of the woman, doxylamine was detected in the proximal segment (0-3 cm) at a concentration of 37 pg/mg. The concentration was compared with those obtained after a single dose and after daily dose administration. In the hair of four subjects receiving a single 15-mg dose and collected 4 weeks later, doxylamine was detected in the proximal segment at 18-52 pg/mg. After daily 15-mg doses for at least 4 months, the hair concentrations of three subjects under doxylamine therapy were 840-2050 pg/mg. © Japanese Association of Forensic Toxicology and Springer 2012.

Kintz P.,X Pertise Consulting | Nicholson D.,DNA Worldwide Group
Forensic Toxicology | Year: 2014

Considering the widespread nature of alcohol-related problems, the diagnosis of excessive alcohol consumption is an important task from medical and legal viewpoints. Alcohol abuse can be documented by usual blood [e.g., carbohydrate deficient transferrin (CDT)] and liver function [e.g., γ-GT or mean corpuscular volume (MCV)] tests, and, over a long-term basis, by hair analysis. Major markers of ethanol consumption in hair are ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). Detection of EtG in hair is said to be associated with excessive alcohol consumption, whereas a negative result does not unambiguously exclude alcohol abuse. Investigations on FAEEs can also be used to monitor excessive alcohol consumption. Four FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate) are the most suitable markers for the detection of heavy alcohol consumption and show different concentrations in hair of children, adult teetotalers, and social drinkers in comparison with FAEEs concentrations found in the hair of alcoholics. The Society of Hair Testing has provided guidelines for hair testing for chronic excessive alcohol consumption, and states positive cutoffs for a 0-3 cm hair segment as 30 pg/mg and 0.5 ng/mg for EtG and FAEEs, respectively. This study reviews the difficulties in interpreting blood and hair results of a 41-year-old woman involved in a child custody legal dispute. Her EtG and FAEEs concentrations in a 0-3 cm segment were 203 pg/mg and 0.29 ng/mg, respectively, and blood parameters were in the normal range (0.6 %, 93 fl, 14 IU/l for CDT, MCV, and γ-GT, respectively). Although the high EtG concentration suggested excessive drinking behavior, the second hair marker, FAEEs, and the three bloods tests were inconspicuous and in accordance with the claim of abstinence from alcohol by the subject. The woman declared having dyed her hair more than 6 months prior to sampling, use of weight-loss medication, and consumption of about four energy drinks per day. A hair lotion based on ethanolic plant extracts was regularly used by the subject, and could have been a source of contamination. Therefore, we recommend that possible external sources of hair contamination always be taken into consideration, especially if contradictory biological results are obtained and if the subject denies any alcohol intake. © 2013 Japanese Association of Forensic Toxicology and Springer Japan.

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