Pharmacokinetic and toxicological evaluation of AB-CHMINACA in rodents: A comprehensive study

Abstract

Objective

This study aimed to develop and validate a sensitive analytical method for detecting and quantifying AB-CHMINACA, and to comprehensively evaluate its pharmacokinetics, metabolic pathways, and acute toxicity in rodent models.

Methodology

Male Wistar rats and Swiss albino mice were used for pharmacokinetics, metabolism, and acute toxicity studies. AB-CHMINACA was dissolved in Dimethyl sulfoxide (DMSO; 2%–5%) and diluted in corn oil for oral gavage. Blood and urine samples were collected from rats for pharmacokinetic and metabolite analyses using Gas Chromatography–Tandem Mass Spectrometry (GC-MS/MS) and liquid chromatography–quadrupole time-of-flight mass spectrometry, respectively. Mice were monitored for behavioral toxicity and necropsied for histopathological analysis. Pharmacokinetic parameters were calculated using WinNonlin Phoenix 6.0, and metabolites were identified through mass spectrometry.

Results

Method validation showed excellent linearity (0.5–1000 ng/mL, r² > .99), with precision (variability 2.3%–7.2%) and accuracy (95%–105%), adhering to FDA guidelines. The method’s limit of detection (LOD) and limit of quantification (LOQ) were 0.5 and 1.0 ng/mL, respectively. Pharmacokinetic analysis revealed a biphasic elimination (t½ 13.8 h), Vd of 228.75 L, and Cl of 11.4 L/h. Four major Phase I metabolites were identified, with Met 4 (Di-Hydroxy-AB-CHMINACA) being the most abundant in urine at 8–24 h. Acute toxicity in mice showed dose-dependent symptoms, including lethargy, seizures, and mortality at 50 mg/kg.

Conclusion

These results enhance the understanding of AB-CHMINACA's pharmacokinetic behavior and metabolic profile, contributing valuable insights to forensic toxicology and highlighting the dose-dependent nature of its acute toxicity.