Incorporation of Zolpidem into Hair and Its Distribution after a Single Administration
Incorporation of Zolpidem into Hair and Its Distribution after a Single Administration
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DOI：
10.1124/dmd.116.074211
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发表时间：
2017-03-01
影响因子：
3.9
通讯作者：
Katagi, Munehiro
中科院分区：
文献类型：
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作者：
Shima, Noriaki;Sasaki, Keiko;Katagi, Munehiro
为了获得药物进入毛发的基本信息，在单次口服唑吡坦（ZP）（最常用的催眠药物之一）后，观察药物沿单束头发分布的时间变化。使用经过验证的LC-MS/MS程序对每根单链头发进行1毫米片段的定量切片头发分析。在单次给药后10和24小时，所有拔毛标本均检测到ZP，其分布范围为整个毛根（长度为4 ~ 5min）。在这些样品的毛球区域检测到高浓度的ZP，而在发根上部广泛观察到低浓度的ZP；这表明ZP的掺入发生在两个区域，主要在毛球区，少量在真皮上区。单次给药后，zp阳性区形成长达10-12 mm的长度，表明其从毛球中融入将持续约2周。发根中ZP浓度的时间变化还表明，随着头发的生长，只有一小部分最初集中在毛球中的ZP逐渐进入毛基质，并向角质化区域移动。在讨论基于毛发分析的个人用药史时，应考虑到这些发现。采用基质辅助激光解吸/电离质谱法对同类毛发样品中的ZP进行了分析。
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 (4-5mmin 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.