The acute oral toxicity and pharmacokinetic determination of a novel chloroquinoline hybrid molecule by LC-MS/MS.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2025-09-30 DOI:10.1080/17576180.2025.2567227

Monique Labuschagne, Makhotso Lekhooa, Thrineshen Moodley, Chakes Mashaba, Matshawandile Tukulula

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引用次数: 0

Abstract

Background: CB-1 is a novel compound evaluated in Sprague Dawley rats to assess its acute oral safety and pharmacokinetic disposition.

Objectives: To determine the short-term oral toxicity of CB-1 and characterize its pharmacokinetic parameters.

Methods: Acute oral toxicity was tested at doses up to 100 mg/kg. For pharmacokinetics, six rats received a single 100 mg/kg oral dose. Plasma samples were analyzed using a polar C18 column and quantified by LC - MS/MS monitoring the 490.063→262.00 m/z transition.

Results: No mortality occurred at 100 mg/kg, indicating acceptable acute safety. CB-1 reached a peak plasma concentration (C_max) of 4324.24 ng/mL at 1 h (T_max1). Pharmacokinetic analysis revealed an apparent clearance (Cl/F) of 3.6 L/h, elimination half-life (t_1/2) of 7.86 h, and volume of distribution (Vd/F) of 40 L. A secondary plasma concentration peak at 8 h (T_max2) suggested enterohepatic recirculation.

Conclusions: CB-1 demonstrated short-term oral safety with rapid absorption, relatively low clearance, and prolonged systemic exposure, likely influenced by enterohepatic recirculation.

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一种新型氯喹啉杂化分子的急性口服毒性及药代动力学的LC-MS/MS测定。

背景：CB-1是一种新型化合物，在Sprague Dawley大鼠中评估其急性口服安全性和药代动力学倾向。目的：测定CB-1的短期口服毒性，并对其药动学参数进行表征。方法：以100mg /kg剂量进行急性口服毒性试验。在药代动力学方面，6只大鼠接受单次100 mg/kg口服剂量。血浆样品采用极性C18色谱柱分析，LC - MS/MS监测490.063→262.00 m/z跃迁。结果：100 mg/kg剂量下无死亡发生，急性安全性可接受。1 h时CB-1血药浓度（Cmax）峰值为4324.24 ng/mL （Tmax1）。药代动力学分析显示，其表观清除率（Cl/F）为3.6 L/h，消除半衰期（t1/2）为7.86 h，分布体积（Vd/F）为40 L。第8小时的二次血药浓度峰值（Tmax2）提示肠肝再循环。结论：CB-1具有短期口服安全性，吸收迅速，清除率相对较低，长期全身暴露，可能受肠肝再循环影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.