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

采用液相色谱-串联质谱法测定一种新型氯喹啉杂合分子的急性口服毒性和药代动力学

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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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