Incorporation of Methoxyphenamine into Hair in Early Stage after Intake

Abstract

In order to investigate the incorporation behavior of drugs into hair in early stage (within 24 h) after intake, time-course changes in drug distribution in black hair were carefully analyzed after a single oral administration of methoxyphenamine (MOP), a non-regulated analog of methamphetamine. Single-hair specimens collected by plucking with the roots intact at appropriate intervals post-intake were each divided into 1-mm segments from the proximal end, and MOP in each segment was determined by a validated liquid chromatography-tandem mass spectrometry procedure. At 10 min after intake, MOP was not detected in any of the segments. MOP became detectable 30 min after intake in the hair bulb (0–1-mm segment from the proximal end) and 1 h after intake in the upper dermis zone (1–2-mm to 4–5-mm segments). The amount of MOP in the hair bulb increased rapidly over 3 h after intake and reached a maximum concentration of about 100–900 pg/1-mm single hair (11–95 ng/mg) around 3–10 h after intake, whereas that in the upper dermis zone increased at a more gradual pace over 24 h and reached a plateau at about 30–100 pg/1-mm hair (3–11 ng/mg). These differences can be attributed to their different incorporation mechanisms. Results from this study can further elucidate the drug incorporation mechanism, which is crucial for accurately interpreting results in hair analyses. Our findings also suggest that hair drugs analysis with special attention to the hair root can serve as a useful complementary approach to urine- and blood-based testing in the field of forensic toxicology.

Time course of estazolam in single-strand hair based on micro-segmental analysis after controlled oral administration

“…These findings indicated the occurrence of two major drug incorporation sites: the hair bulb and the upper dermis zone of the hair root. Two drug peaks in hair were also reported in other studies for zolpidem and methoxyphenamine after a single dose ( Shima et al, 2017 ; Nitta et al, 2021 ).…”

“…Estazolam took a longer time to achieve a peak level in the hair bulb than in the plasma, suggesting that estazolam was gradually accumulated in the hair bulb region after a single administration. Similar findings have been reported for methoxyphenamine, which showed rapid increases in plasma that reached maximum concentrations 1 h after intake but only became detectable in hair 30 min after intake in the hair bulb (0-1 mm) and 1 h after intake in the upper dermis zone (2-4 mm) (Nitta et al, 2021).…”

“…The time course of estazolam incorporation in the hair root in the short timeframe (i.e., 24 h) following intake would be key in unveiling the mechanism of its incorporation into hair ( Nitta et al, 2021 ). At 12 h after intake, the highest amounts of estazolam were localized in the 0–0.4 mm segment (S1) that included the hair bulb, along with a small fluctuation that appeared at the junction of the hair root and shaft (S4–S7).…”

“…Highly lipophilic compounds, such as zolpidem, are incorporated mainly through Region 1, whereas the sweat/sebum route might be more dominant than the blood route for the uptake of highly polar compounds, such as ethyl glucuronide, into hair ( Schräder et al, 2012 ). Compounds with average basicity and lipophilicity, such as methoxyphenamine, would be incorporated into both regions at comparable levels ( Nitta et al, 2021 ).…”

“…The incorporation pathways of drugs into hair have been clarified by several researchers who have analyzed substances/metabolites in plucked hairs after single doses of a drug/substance of interest ( Miki et al, 2011 ; Schräder et al, 2012 ; Kamata et al, 2015 ; Shima et al, 2017 ; Shima et al, 2019 ; Kamata et al, 2020 ; Nitta et al, 2021 ). For example, Shima et al ( Shima et al, 2017 ) revealed that zolpidem is incorporated into two regions of the hair root ( Figure 1 ).…”