Neuwiller-lès-Saverne, France
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Kintz P.,X Pertise Consulting | Kintz P.,Institute Of Medecine Legale
Forensic Science International | Year: 2015

Hair specimen is necessary to complement blood and/or urine analyses as it permits differentiation of a single exposure from chronic use of a drug by segmentation of the hair for a stated growth period. Moreover, due to a frequent long delay between event and police declaration, hair can be the only solution for lack of corroborative evidence of a committed crime. With the exception of lower amount of biological material in children versus adults, there is no specific analytical problem when processing samples from children. The issue is the interpretation of the findings, with respect to the different pharmacological parameters. In some very young children, the interpretation can be complicated by potential in utero exposure.Twenty-four cases from daily practice have been reviewed. Children were less than 1 year old, hair was always longer than 4. cm and the corresponding mothers admitted having used drugs during pregnancy.Drugs involved include methadone, tramadol, diphenhydramine, diazepam, cannabis, heroin, amitriptyline and bromazepam. Analyses were achieved by hyphenated chromatographic validated procedures after hair decontamination and segmentation.The concentrations measured in the hair of children were lower than those observed in subjects using therapeutically (or illegally) these drugs. In that sense, the frequency of exposures appears as un-frequent (low level of exposure), with marked decrease in the more recent period. However, the parents denied any administration in all cases and there was no reason to suspect re-exposure after delivery and no clinical problem during the period between delivery and hair collection during regular visits to the physician was noticed. The pattern of drug distribution was similar in all these cases, low concentrations in the proximal segments and highest concentration in the distal segment (last segment). When considering the concentration in the distal segment as the 100% of the response (highest concentration), after analysis of 4 segments (irrespective of the length of the segment but longer than 1. cm), it was observed the following pattern: proximal segment, 5-35% of the response; segment 2, 15-50% of the response; segment 3, 25-60% of the response; and distal segment, 100% of the response.It is proposed to consider 100% in utero contribution to the final interpretation when the ratio concentration of the proximal segment to the concentration of the distal segment is lower than 0.5. This can be applied only when the child is under 1 year old and the hair shaft length is at least 4. cm (to achieve suitable segmentation). It is important, when using this cut-off to have at least 3 or 4 segments to be able to observe the variation in drug concentrations, whatever the length of each segment (>1. cm). © 2014 Elsevier Ireland Ltd.


Chatterton C.,Forensic Science Service | Kintz P.,X Pertise Consulting
Journal of Forensic and Legal Medicine | Year: 2014

Amitriptyline, temazepam, tramadol and dihydrocodeine are prescription-only-medications that are rarely prescribed to children. Each of these drugs has a sedative effect on the central nervous system; their combined use could cause an exacerbation of the sedative effects. Amitriptyline (a tricyclic antidepressant) can be prescribed to treat nocturnal enuresis; temazepam (a hypnotic) can be used as a premedicant in inpatient and day-case surgery; tramadol (a synthetic opioid analgesic) is used to treat moderate or severe pain, though it is not recommended for children under the age of 12 years and dihydrocodeine (opioid analgesic), which is available in combination with acetaminophen (Co-dydramol®), is not recommended for children under the age of 4 years; in children over 4 years, a reduced dose is necessary. The North West Forensic Science Service Laboratory, Euxton, Lancashire, was asked by a British police force to analyze three separate hair samples, which had been collected from a young child following their discovery as a result of a large scale kidnap and false imprisonment investigation. After decontamination and segmentation (20 x 1-cm section), two of the three hair specimens were analyzed by liquid chromatography coupled with tandem mass spectrometry after alkaline (pH 9.5) extraction using methylene chloride/isopropanol/n-heptane (25:10:65, v/v/v). The entire length of each hair specimen tested positive for amitriptyline and nortriptyline (7-314 pg/mg amitriptyline; 7-318 pg/mg nortriptyline), temazepam (2-29 pg/mg), tramadol (60-2000 pg/mg) and dihydrocodeine (10-90 pg/mg) demonstrating that the child had ingested these drugs on more than one occasion prior to the kidnap. In this case, the child's mother and the mothers' partner were found guilty of kidnap, false imprisonment and perverting the course of justice. There are very few studies citing the concentrations of these drugs in children - especially children's hair samples. This case demonstrates the added value of hair testing and emphasizes the importance of using hair samples to complement conventional analysis. © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.


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

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 | 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.


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

The influence on drug incorporation of melanin affinity, lipophilicity, and membrane permeability is of paramount importance. Despite their high lipophilicity, some drugs have quite low incorporation rate into hair, suggesting that the higher incorporation rates of basic drugs (cocaine, amphetamines.) than neutral (steroids, benzodiazepines, cannabinoids...) or acidic ones are strongly related to the penetrating ability of the drug to break through the membrane based on the pH gradient between blood and the acidic hair matrix. When using hair analysis as a matrix during investigative analysis, e.g. workplace drug testing, doping, driving under the influence, drug-facilitated crime, the question of importance is to know whether the analytical procedure was sensitive enough to identify traces of drugs; this is particularly important when the urine sample(s) of the subject was positive and the hair sample(s) was negative. It has been accepted in the forensic community that a negative hair result cannot exclude the administration of a particular drug, or one of its precursors and the negative findings should not overrule a positive urine result. Nevertheless, the negative hair findings can, on occasion, cast doubt on the positive urine analysis, resulting in substantial legal debate and various consequences for the subject. The concept of minimal detectable dosage in hair is of interest to document the negative findings, but limited data is currently available in the scientific literature. Such data includes cocaine, codeine, ketamine, some benzodiazepines and some unusual compounds. Until laboratories will have sensitive enough methodologies to detect a single use of drug, care should be taken to compare urine and hair findings. © 2011 Elsevier Ireland Ltd.


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

The hair of 97 cases were analysed for ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE, including ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) according to the Society of Hair Testing guidelines to examine the role of both tests in documenting chronic excessive alcohol drinking, particularly when the results are in contradiction. 27 (27.8%) results were EtG negative and FAEE positive, when applying the SoHT cut-offs, probably due to the use of alcohol-containing hair products. Four cases (4.1%) were EtG positive and FAEE negative that were attributed to the use of herbal lotions containing EtG. © 2014 Elsevier Ireland Ltd.


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

Excluding laboratory mistakes, a false positive hair result can be observed in case of contamination from environmental pollution (external contamination) or after drug incorporation into the hair from the individual body fluids, such as sweat or putrefactive fluid (post mortem artifact). From our 20 years experience of hair testing, it appears that artifact(s) cannot be excluded in some post mortem cases, despite a decontamination procedure. As a consequence, interpretation of the results is a challenge that deserves particular attention. Our strategy will be reviewed in this paper, based on six cases. In all cases, a decontamination procedure with two washes of 5. ml of dichloromethane for 5. min was performed and the last dichloromethane wash was negative for each target drug. From the histories, there was no suspicion of chronic drug use. In all six cases, the concentrations detected were similar along the hair shaft, irrespective of the tested segment. We have considered this as indicative of external contamination and suggested to the forces or the judges that it is not possible to indicate exposure before death. In contrast to smoke, it seems that contamination due to aqueous matrices (sweat, putrefactive fluid, blood) is much more difficult to remove. To explain potential incorporation of 7-aminoflunitrazepam via putrefactive material, the author incubated negative hair strands in blood spiked at 100. ng/ml and stored at +4 °C, room temperature and +40 °C for 7, 14 and 28 days. After routine decontamination, 7-aminoflunitrazepam tested positive in hair, irrespective of the incubation temperature, as early as after 7 days (233-401. pg/mg). In all periods, maximum concentrations were observed after incubation at room temperature. The highest concentration (742. pg/mg) was observed after 28 days incubation at room temperature. It is concluded that a standard decontamination procedure is not able to completely remove external contamination in case of post mortem specimens. Homogenous segmental analyses can be probably indicative of external contamination and therefore a single hair result should not be used to discriminate long-term exposure to a drug. Nor should the presence of a metabolite be considered as a discrimination tool, as it can also be present in putrefactive material. © 2011 Elsevier Ireland 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.

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