Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes

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Recent studies indicate that not only the anthelminthic levamisole but also the racemate tetramisole (R-/S-phenyltetraimidazothiazole, PTHIT) was found as an adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine-positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine-positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n = 724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). For distinction of levamisole/dexamisole chiral LC-MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut-off) to approximately 800 000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT-adulterated street cocaine samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non-racemic PTHIT.Our experiments suggest that the presence of tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also tetramisole and terminology in scientific contributions should be used accordingly.

Section: Analysis Of Sheep Wool Samples Following Levamisole Adminimentioning

confidence: 99%

Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long‐term monitoring of its intake by chiral LC–MS/MS analysis of cocaine‐positive hair samples

Madry

Kræmer

Baumgartner

2018

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“…[14] Therefore, homogenization is required before drug extraction. [14] Therefore, homogenization is required before drug extraction.…”

Section: Discussionmentioning

confidence: 99%

“…[14] They used 20 mg of 1 cm hair segments, which corresponds to several hundred hairs, for the segmental analysis and showed that the analytical results roughly reflected the time of drug intake. If all tested hairs grow at 1 cm/month, segments 2-2 and 3-3 must have the maximum concentrations of all analytes at the respective sampling times.…”

Section: Drug Concentrations In Hair and Nailsmentioning

confidence: 99%

Time‐course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products

Kuwayama

Miyaguchi

Iwata

et al. 2016

Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd.

“…described the stereoselective determination of 3,4‐methylendioxymethamphetamine (MDMA) and its metabolites in human blood plasma by chiral derivatization with N ‐(2,4‐dinitro‐5‐fluorophenyl)‐L (S) ‐valinamide (DNPV) and LC separation . Madry et al applied the same method to analyze MDMA and 3,4‐Methylendioxyamphetamine (MDA) incorporation into hair and nail segments . The goal of our study was the development and validation of a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method employing chiral derivatization for the determination of (R)‐ and (S)‐ amphetamine in hair.…”

Section: Introductionmentioning

confidence: 99%

“…16 Madry et al applied the same method to analyze MDMA and 3,4-Methylendioxyamphetamine (MDA) incorporation into hair and nail segments. 17 The goal of our study was the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employing chiral derivatization for the determination of (R)and (S)-amphetamine in hair. The validated method should then be applied to the analysis of authentic hair samples and a controlled lisdexamfetamine and dexamphetamine administration study to evaluate its usefulness and reliability for compliance monitoring and differentiation of patients taking the drug Elvanse® and street amphetamine users.…”

mentioning

confidence: 99%

Chiral analysis of amphetamines in hair by liquid chromatography–tandem mass spectrometry: compliance‐monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low‐dose application

Binz

Williner

Strajhar

et al. 2017

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Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high-pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug-facilitated crime (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine.