Measurement of three-dimensional distributions of drugs in nails using liquid chromatography/tandem mass spectrometry after micro-segmentation to elucidate drug uptake routes
Measurement of three-dimensional distributions of drugs in nails using liquid chromatography/tandem mass spectrometry after micro-segmentation to elucidate drug uptake routes
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DOI：
10.1016/j.aca.2020.02.050
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发表时间：
2020-04-29
影响因子：
6.2
通讯作者：
Iwata, Yuko T.
中科院分区：
文献类型：
--
作者：
Kuwayama, Kenji;Miyaguchi, Hajime;Iwata, Yuko T.
摄入的药物可以从血液中进入指甲和头发，这些药物可以稳定地保留几个月或更长时间。游离的指甲边缘通常可以作为样本来证明药物摄入。然而，药物进入指甲的机制尚不清楚。虽然假设甲根处存在水平吸收途径，甲床处存在与生长方向相反的垂直吸收途径，但这一现象需要通过三维分布分析来验证。在此，我们首次开发了一种结合指甲微分割（0.2 x 1.5 x 0.06 mm）和LC-MS/MS高灵敏度药物定量的方法来测量指甲中药物的三维分布。研究人员将卡比诺胺作为一种模型化合物，单次给受试者服用，然后在一年的时间里，每隔几周收集一次大趾甲的游离边缘。卡比诺胺在每个自由边的三维分布可视化，并沿采集周期排列。卡比诺胺在采集初期（服药后78天）集中在下层，在采集后期（服药后134天）集中在上层和中层。药物在甲内沿收集期分布的变化表明，药物在整个甲内同时通过甲床和甲根进行双向摄取。所建立的分析方法有助于阐明药物进入指甲的吸收机制。(C) 2020 Elsevier B.V.版权所有
Ingested drugs can be taken up into nails and hairs from the bloodstream and these drugs can be stably retained over several months or more. Free edges of nails can often be used as a specimen to prove drug intake. However, the mechanism of drug uptake into the nails is unclear. Although it is presumed that there are horizontal uptake routes at the nail root and vertical uptake routes at the nail bed against the direction of growth, three-dimensional distribution analysis is required to verify this phenomenon. Herein, we first developed a method to measure the three-dimensional distribution of drugs in the nails using the combination of micro-segmentation of nails (0.2 x 1.5 x 0.06 mm size) and highly sensitive quantification of drugs by LC-MS/MS. Carbinoxamine was administered as a model compound to a subject in a single dose, and then the free edges of big toenails were collected every several weeks over a year. The three-dimensional distribution of carbinoxamine in each free edge was visualized and arranged along the collection period. Carbinoxamine was localized in the lower layer during the early collection period (up to 78 days after drug ingestion) and in the upper and middle layers later (134 days or later). The changes in the drug distribution in the nails along the collection period implied that two-way drug uptake takes place in the whole nail through both the nail bed and the nail root simultaneously. The developed analytical method could be useful to elucidate the mechanism of drug uptake into the nails. (C) 2020 Elsevier B.V. All rights reserved.