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不同链长苯扎氯铵经静脉注射在大鼠体内的动力学和分布。

Kinetics and distribution of benzalkonium compounds with different alkyl chain length following intravenous administration in rats.

机构信息

Department of Legal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama, Kanagawa 236-0004, Japan.

Department of Legal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama, Kanagawa 236-0004, Japan.

出版信息

Leg Med (Tokyo). 2021 Feb;48:101821. doi: 10.1016/j.legalmed.2020.101821. Epub 2020 Nov 25.

DOI:10.1016/j.legalmed.2020.101821
PMID:33348260
Abstract

Benzalkonium chloride is widely used in disinfectants. Several toxicological and fatal cases have been reported; however, little is known about its kinetics and distribution. We investigated the kinetic characteristics and distribution of benzalkonium cation (BZK) based on the length of the alkyl chains C12, C14, and C16. Rats were treated intravenously with BZK solution (dose, 13.9 mg/kg) containing equal amounts of the three homologues. Kinetic parameters in the blood were assessed, and BZK distribution in the blood and tissues was examined both in rapid intravenous (IV) and drip intravenous (DIV) administrations. BZK concentrations were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). BZK with longer alkyl chains showed lower elimination tendencies and remained in the blood for a longer duration. Concentrations of BZK were higher in the heart, lung, spleen, and kidney than those in the blood, and lower in the brain and fat. In both the IV and DIV groups, the lung, liver, spleen, and fat samples showed higher concentrations of the longer alkyl chains (BZK-C12 < -C14 < -C16), and the opposite trend was observed in the kidney (BZK-C16 < -C14 < -C12). Only the heart and muscle samples displayed the homologues in ratios comparable to the original administered solutions. Differences between IV and DIV groups could be identified by comparing concentrations of BZK homologues in the heart, lung, spleen, and kidney samples. We found that the kinetics and distribution of BZK were influenced by the alkyl chain length, and analysing each BZK homologues in blood and tissue samples may provide useful information.

摘要

苯扎氯铵广泛应用于消毒剂。已有几例毒理学和致命病例报告,但对其动力学和分布知之甚少。我们基于碳链长度 C12、C14 和 C16 研究了苯扎铵阳离子(BZK)的动力学特征和分布。大鼠静脉内给予含有等量三种同系物的 BZK 溶液(剂量为 13.9mg/kg)。评估血液中的动力学参数,并在快速静脉内(IV)和滴注静脉内(DIV)给药后检查 BZK 在血液和组织中的分布。通过液相色谱-串联质谱法(LC-MS/MS)分析 BZK 浓度。具有较长烷基链的 BZK 显示出较低的消除趋势,并且在血液中停留的时间更长。BZK 在心脏、肺、脾和肾中的浓度高于血液中的浓度,而在大脑和脂肪中的浓度较低。在 IV 和 DIV 组中,肺、肝、脾和脂肪样本中较长烷基链(BZK-C12 < -C14 < -C16)的浓度较高,而肾脏中则相反(BZK-C16 < -C14 < -C12)。只有心脏和肌肉样本显示出与原始给药溶液相当的同系物比例。通过比较心脏、肺、脾和肾样本中 BZK 同系物的浓度,可以区分 IV 和 DIV 组之间的差异。我们发现 BZK 的动力学和分布受烷基链长度的影响,分析血液和组织样本中的每个 BZK 同系物可能提供有用的信息。

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