Hilke Andresen-Streichert

Determination of ethyl glucuronide in hair improves evaluation of long-term alcohol abstention in liver transplant candidates.

Prior to listing patients for Orthotopic liver transplantation (OLT) an abstention period of 6 months is required. Ethyl glucuronide in the hair is a new reliable marker for the assessment of alcohol consumption. Here, the diagnostic value of determining the ethyl glucuronide concentration in the hair of liver transplant candidates was evaluated.

Methadone and illegal drugs in hair from children with parents in maintenance treatment or suspected for drug abuse in a German community.

Background: Children living in homes with drug-addicted parents are in a steady danger of poisoning and may suffer from neglect, maltreatment, and lagging behind in development. Hair analysis could be a suitable way to examine this endangering exposure to drugs. Methods: Hair samples from 149 children (aged 1–14 years) living with parents substituted by methadone and/or suspected for abuse of illegal drugs, and from 124 of the parents in a German community were investigated by liquid chromatography-hybrid quadrupole time-of flight mass spectrometry and by headspace solid phase microextraction gas chromatography-mass spectrometry for methadone, heroin, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines and their metabolites or degradation products (32 compounds). Results: From the childrens hair, only in 35 samples, no drugs were detected. Cannabinoids were found in 56 samples, in 20 of them as the only drug. In the remaining 95 samples, methadone was identified 35 times with additional use of illegal drugs in 28 cases. Drug use in the childrens environment was obvious for heroin in 44 cases, cocaine in 73 cases, amphetamine or ecstasy in 6 cases, and diazepam in 8 cases. The concentrations varied from limit of quantification to 2.16 ng/mg of methadone, 11.1 ng/mg of 6-acetylmorphine, 17.8 ng/mg of cocaine, 3.29 ng/mg of amphetamine, and 0.72 ng/mg of &Dgr;9-tetrahydrocannabinol. In general, hair from younger children contained higher concentrations than from their elder siblings. Systemic incorporation of methadone, cocaine, or cannabinoids appeared likely from detection of the nonhydrolytic metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in 11 cases, norcocaine in 16 cases, and 11-nor-9-carboxy-&Dgr;9-tetrahydrocannabinol in 9 cases. Within the families, hair samples of children and parents provided often the same drug pattern. External deposition from smoke and by contact with contaminated surfaces or parents hands and systemic deposition after passive smoking, administration, or oral intake by hand-to-mouth transfer were discussed as alternative incorporation mechanisms into hair. Conclusions: Altogether, investigation of childrens hair proved to be a useful way to detect endangering drug use in their environment and lead to a more thorough inspection and measures to improve their situation in many of the cases.

Analysis of cyclosporin a in hair samples from liver transplanted patients.

Introduction: Cyclosporin A (CsA) is one of the most important immunosuppressants currently used to prevent organ rejection after liver transplantation. Therapeutic benefit and adverse toxicity are associated with only small differences in CsA blood concentration. Correct individual dosage and compliance are therefore essential for successful therapy. To this end, we developed a validated analytical assay for the determination of CsA in hair samples. Hair samples from patients treated with CsA after liver transplantation were analyzed to investigate correlations between hair concentrations, blood concentrations, and CsA doses. The aim of this study was to evaluate whether hair analysis could be useful for the long-term follow-up of liver transplantation patients. Materials and Methods: Hair samples from patients were segmented and decontaminated. After alkaline hydrolysis and liquid–liquid extraction, CsA was analyzed by liquid chromatography–tandem mass spectrometry. Results: The peptide CsA (molecular weight 1202.6 Da) was detected in all the patient hair segments corresponding to times of CsA intake, whereas all hair segments reflecting times without CsA treatment tested negative. Correlation between CsA hair concentrations and CsA doses was poor. Consequently, it was not possible to verify the amount of CsA intake by hair analysis. A correlation coefficient of r2 = 0.57 was found for the correlation of average whole blood trough concentrations and hair concentrations. The segmental CsA hair concentrations were found to be much steadier than the whole blood trough concentrations. In patients with stable or slightly changed CsA dosages, a comparable segmental concentration profile with a decrease in CsA hair concentrations from proximal to distal was found. Major modifications in CsA dosage are followed by a corresponding trend in segmental hair concentrations. Conclusions: Our results suggest that it is not possible to quantify the amount of CsA intake by hair analysis. Segmental hair analysis might be useful in the detection of substantial noncompliance and to detect changes in drug-taking behavior.

Determination of ethyl glucuronide in human hair samples: A multivariate analysis of the impact of extraction conditions on quantitative results

BACKGROUND Ethyl glucuronide (EtG), a minor metabolite of ethanol, is used as a direct alcohol biomarker for the prolonged detection of ethanol consumption. Hair testing for EtG offers retrospective, long-term detection of ethanol exposition for several months and has gained practical importance in forensic and clinical toxicology. Since quantitative results of EtG hair testings are included in interpretations, a rugged quantitation of EtG in hair matrix is important. As generally known, sample preparation is critical in hair testing, and the scope of this study was on extraction of EtG from hair matrix. METHODS The influence of extraction solvent, ultrasonication, incubation temperature, incubation time, solvent amount and hair particle size on quantitative results was investigated by a multifactorial experimental design using a validated analytical method and twelve different batches of authentic human hair material. Eight series of extraction experiments in a Plackett-Burman setup were carried out on each hair material with the studied factors at high or low levels. The effect of pulverization was further studied by two additional experimental series. Five independent samplings were performed for each run, resulting in a total number of 600 determinations. RESULTS Considerable differences in quantitative EtG results were observed, concentrations above and below interpretative cut-offs were obtained from the same hair materials using different extraction conditions. Statistical analysis revealed extraction solvent and temperature as the most important experimental factors with significant influence on quantitative results. The impact of pulverization depended on other experimental factors and the different hair matrices themselves proved to be important predictors of extraction efficiency. CONCLUSIONS A standardization of extraction procedures should be discussed, since it will probably reduce interlaboratory variabilities and improve the quality and acceptance of hair EtG analysis.

Uptake of Gamma-Valerolactone—Detection of Gamma-Hydroxyvaleric Acid in Human Urine Samples

Gamma-valerolactone (GVL) is reported to be a substance that can be used as a legal substitute for gamma-hydroxybutyric acid (GHB), which is currently a controlled substance in several countries. Unlike gamma-butyrolactone and 1,4-butanediol, GVL is not metabolized to GHB, which causes the effects after uptake of these two chemicals. In the case of GVL, the lactone ring is split to gamma-hydroxyvaleric acid (GHV or 4-methyl-GHB) by a lactonase. Because of its affinity for the GHB receptor, GHV reveals similar effects to GHB, although it is less potent. Intoxications with GVL, or its use as a date rape drug, are conceivable. Despite these facts, there are no publications in the literature regarding detections of GHV in human samples. This study reports three cases, including five urine samples, in which GHV could be detected in concentrations between 3 and 5.8 mg/L. In one of these cases, a drug-facilitated sexual assault (DFSA) was assumed; four of these samples were from two people suspected of abusing GHB. The results indicate that GVL is used as an alternative to GHB and its precursors and should be taken seriously. GVL or GHV should be included in toxicological analysis, particularly in DFSA cases. More information is needed regarding the pharmacokinetics of GVL/GHV for the meaningful interpretation of positive or negative results.

Improved detection of alcohol consumption using the novel marker phosphatidylethanol in the transplant setting: results of a prospective study

Phosphatidylethanol (PEth) is a new, highly specific alcohol marker. The aim of this study was to assess its diagnostic value in the liver transplant setting. In 51 pre‐ and 61 post‐transplant patients with underlying alcoholic liver disease PEth, ethanol, methanol, carbohydrate‐deficient transferrin (CDT), and ethyl glucuronide in urine (uEtG) and hair (hEtG) were tested and compared with patients’ questionnaire reports. Twenty‐eight (25%) patients tested positive for at least one alcohol marker. PEth alone revealed alcohol consumption in 18% of patients. With respect to detection of alcohol intake in the preceding week, PEth showed a 100% sensitivity. PEth testing was more sensitive than the determination of ethanol, methanol, CDT or uEtG alone [sensitivity 25% (confidence interval (CI) 95%, 7–52%), 25% (7–52%), 21% (6–45%) and 71% (41–91%), respectively], or ethanol, methanol and uEtG taken in combination with 73% (45–92%). Specificity of all markers was 92% or higher. Additional testing of hEtG revealed alcohol consumption in seven patients, not being positive for any other marker. Phosphatidylethanol was a highly specific and sensitive marker for detection of recent alcohol consumption in pre‐ and post‐transplant patients. The additional determination of hEtG was useful in disclosing alcohol consumption 3–6 months retrospectively.

Correction to: Mass poisoning with NPS: 2C-E and Bromo-DragonFly

The original version of this article contains an error. The Author S. Lehmann incorrectly listed as S. Lehman. The correct spelling is presented above. The original article has been corrected.

Attempted Drug-facilitated Sexual Assault-Xylazine Intoxication in a Child.

There are only a few cases of drug‐facilitated sexual assaults on children reported in the literature so far. Here, a case of a four‐year‐old boy is presented. He was unconscious, and the accompanying adults reported that the child had been at a playground on his own. Returning home, he complained of having been stung and collapsed immediately. Urine and serum samples of the child were investigated. In the toxicological analysis, xylazine, a sedative and muscle relaxant used in animals, was detected. Subsequent quantification by GC/MS after solid‐phase extraction revealed 0.053 mg/L xylazine in serum and approximately 0.63 mg/L in urine. Furthermore, the child was examined by a forensic medical specialist. Police investigations revealed that the godfather, who had been previously accused of sexual abuse of children, had injected the child with the drug, possibly in preparation for a shared bath.