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

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 (Cmax) of 4324.24 ng/mL at 1 h (Tmax1). Pharmacokinetic analysis revealed an apparent clearance (Cl/F) of 3.6 L/h, elimination half-life (t1/2) of 7.86 h, and volume of distribution (Vd/F) of 40 L. A secondary plasma concentration peak at 8 h (Tmax2) 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.