Incorporation of Zolpidem into Hair and Its Distribution after a Single Administration

Abstract

To obtain fundamental information on the drug incorporation into hair, time-course changes in drug distribution along single-strand hair were observed after a single oral administration of zolpidem (ZP), one of the most frequently used hypnotic agents. Quantitative sectional hair analyses of 1-mm segments were performed for each single-strand hair using a validated LC-MS/MS procedure. ZP was detected in all specimens plucked at 10 and 24 hours after a single dose, and the distribution ranged over the whole hair root (4-5 mm in length). A significantly high concentration of ZP was detected in the hair bulb region, whereas much lower concentrations were widely observed in the upper part of the hair root of those samples; this suggested that the incorporation of ZP occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. The ZP-positive area formed lengths of up to 10-12 mm after a single administration, indicating that its incorporation from the hair bulb would continue for about 2 weeks. Time-course changes in the ZP concentration in the hair root additionally revealed that only a small portion of ZP that initially concentrated in the bulb was successively incorporated into the hair matrix and moved toward the keratinized region as hair grew. These findings should be taken into account upon discussing individual drug-use history based on hair analysis. The matrix-assisted laser desorption/ionization mass spectrometry imaging of ZP in the same kinds of hair specimens was also successfully achieved.

Different localizations of drugs simultaneously administered in a strand of hair by micro‐segmental analysis

“…Because the S 1 values for ME and EP were close to the S 2 values for DC and CP, the sweat/sebum route might be more dominant than the blood route for the uptake of ME and EP into hair. Shima et al recently reported, using 1‐mm segments which correspond to a growth length of 2.5 days, that the distributions of zolpidem and methoxyphenamine within a hair strand mapped to 2 regions with high concentrations . Both zolpidem and methoxyphenamine generated 2‐peak profiles, bulb‐origin and dermas‐origin peaks.…”

“…Shima et al recently reported, using 1-mm segments which correspond to a growth length of 2.5 days, that the distributions of zolpidem and methoxyphenamine within a hair strand mapped to 2 regions with high concentrations. 18,19 Both zolpidem and methoxyphenamine generated 2-peak profiles, bulb-origin and dermas-origin peaks. The intensity of dermas-origin peak was comparable to the intensity of bulb-origin peak for methoxyphenamine, while the bulb-origin peak was more dominant than the dermas- The average ± standard deviation (SD) was calculated using values obtained from 20 strands of hair (ie, all strands of hair except for nos.…”

“…Kamata et al previously reported 1‐mm segmental analysis using LC–MS/MS and time‐course analysis using MALDI–IMS of methoxyphenamine in a strand of hair, which was sampled with the root intact . Shima et al also performed the combination of LC–MS/MS and MALDI–IMS for measuring the distribution of zolpidem in a strand of hair …”

“…By contrast, the use of a strand of hair and shorter segments is limited by insufficient detection sensitivity. Although the analysis of a strand of hair using matrix-assisted laser desorption/ionizationimaging mass spectrometry (MALDI-IMS) has resolved the problem of spatial resolution (because the laser spot diameter and step size are normally 100 μm each), [10][11][12][13][14][15][16][17][18][19] MALDI-IMS is inferior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) because the recent development of high-end instruments has improved drug detection sensitivity and quantification in biological samples. [18][19][20] Both high spatial resolution and detection sensitivity are required to measure the distributions of drugs in a strand of hair in detail.…”

“…18 Shima et al also performed the combination of LC-MS/MS and MALDI-IMS for measuring the distribution of zolpidem in a strand of hair. 19 To advance segmental hair analysis using LC-MS/MS, we developed a method to accurately cut a strand of hair at intervals of 0.4 mm, which corresponds to the average daily hair growth length, using a tissue slicer with a micrometer. Moreover, we optimized the method for drug extraction from a 0.4-mm hair segment using short-duration sonication and long-duration soaking in an extraction solution to effectively treat numerous hair segment samples.…”