Systematic investigation of the incorporation mechanisms of zolpidem in fingernails

Abstract

Nails are attracting increasing interest in forensic toxicology as an alternative to hair. The goal of this study was to systematically investigate the incorporation of drugs in fingernails after single drug dose, exemplified for zolpidem. Fingernail samples from ring fingers were collected one week before, and then 24 h and weekly after intake for a period of three to five months. Hair samples were taken six weeks after intake. Nail specimens were pulverized and extracted with methanol (internal standard: zolpidem-D6 ) under sonication. Extracts were analyzed by a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method, which was developed and validated for this study. The lower limit of quantification (LLOQ) for a 5-mg sample was 0.1 pg/mg nail. Zolpidem was detected continuously in fingernail clippings. The mean window of detection of zolpidem in fingernail clippings was 3.5 months. Unwashed nail specimens taken 24 h after intake showed the highest zolpidem concentrations indicating external contamination by sweat. External contamination experiments revealed that zolpidem could be incorporated in fingernails by sweat to such an extent that it remained irremovable by daily hygiene. Averagely 3 months after intake a concentration peak was reached, suggesting outgrowth of the nail part which had been formed while the drug circulated in blood. Hair concentrations were higher than the maximum nail concentrations. Pigmented hair contained more zolpidem than non-pigmented hair from the same strand. From all these results it can be concluded, that fingernail clippings may represent a useful alternative and/or complementary matrix in cases of, for example, drug-facilitated sexual assault or monitoring of constant consumption behavior.

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

“…In two previous studies, it was demonstrated that a single drug dose is detectable in fingernail clippings [20,19]. The present study describes nail findings following two MDMA administrations.…”

“…There was no relationship between drug concentrations in nail samples and days passed after the first or second MDMA intake. Nail incorporation takes place via nail matrix and nail bed [20,19]. In nail clipping drugs can be detected earlier after incorporation via nail bed than via nail matrix.…”

“…It should be noted that hair and nail samples represent different time frames: about 5 months based on an average growth rate if the hair sample is 5 cm long, for nail clippings a median window of detection of 3.5 months was determined [20]. To our knowledge, there is no report on windows of detection for scrapings.…”

“…It is nowadays recognized that drug disposition into hair takes place not only at the hair follicle but also via diffusion from sweat and sebum [1]. Studies on the incorporation pathways into nails were performed after a single dose of zolpidem [19,20]. The germinal nail matrix and nail bed were identified as incorporation regions for drugs.…”

“…The germinal nail matrix and nail bed were identified as incorporation regions for drugs. Furthermore, sweat presumably contributes to a large extent to drug disposition into nail as drug could already be detected in fingernail clippings 24 hours after drug intake [20]. The investigation of drug stereoisomers could hypothetically provide insights into incorporation mechanisms into hair and nail.…”