Determine the pharmacokinetics (half-life, volume of distribution and clearance) of AMB-FUBINACA in rats plasma using GC-MS / MS

Elkhatim Hassan Abdelgadir; Sarah Dafer Alshehri; Sachil Kumar

doi:10.1016/j.vascn.2024.107513

Determine the pharmacokinetics (half-life, volume of distribution and clearance) of AMB-FUBINACA in rats plasma using GC-MS / MS

J Pharmacol Toxicol Methods. 2024 May 9:127:107513. doi: 10.1016/j.vascn.2024.107513. Online ahead of print.

Authors

Elkhatim Hassan Abdelgadir¹, Sarah Dafer Alshehri², Sachil Kumar³

Affiliations

¹ Department of Forensic Science, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh, Saudi Arabia. Electronic address: eelamin@nauss.edu.sa.
² Division of Toxicology, Department of Central Military Laboratory and Blood Bank, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Electronic address: sarah.alshehri@outlook.sa.
³ Amity Institute of Forensic Sciences, Amity University, Noida, Uttar Pradesh, India. Electronic address: skumar63@amity.edu.

PMID: 38729531
DOI: 10.1016/j.vascn.2024.107513

Abstract

Background: Several novel synthetic cannabinoids, including methyl 2-(1-(4-fluorobenzyl)-1Hindazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA), have recently surfaced on the illicit drug market. To determine the pharmacokinetic properties (half-life, volume of distribution, and clearance) of AMB-FUBINACA in rats plasma, a straightforward, quick, and highly sensitive analytical approach was developed.

Methods: Eighteen Wistar rats were divided into two groups: one control (saline vehicle) and one treatment group (AMB-FUBINACA at 50 mg/kg). Blood samples (400 μL) were withdrawn via catheters immediately before (t = 0) and at 30, 60, 90, 120, and 240 min following injection. Samples were collected into 1 mL tuberculin syringes, then transferred to 1.5 mL plastic tubes containing 5 μL of 1000 IU/mL K3-EDTA (Thomas Scientific). Place the EDTA tubes containing samples in a centrifuge and spin at 1000 g for 10 min at 4 °C. The top layer is the plasma fraction, which is decanted into cryovials and stored at -20 °C until analysis. The gas chromatography tandem mass spectrometry (GC-MS/MS) method was optimized and validated, combined with liquid-liquid extraction, to analyze AMB-FUBINACA in rat plasma.

Results: The research method successfully met the validation requirements set by the FDA, demonstrating selectivity and linear calibration curves within a concentration range of 0.5-1000 ng/ml. The correlation coefficient (r2) was determined to be 0.99, indicating a strong linear relationship. The analyte's limit of quantitation (LOQ) was determined to be 1-5 ng/mL. Subsequently, the method was successfully applied to investigate the pharmacokinetics of AMB-FUBINACA in rats' blood samples. Following oral administration, AMB-FUBINACA was rapidly absorbed, with a plasma half-life (t1/2) of 5.91 h, a volume of distribution (Vd) of 203.13 l, and a plasma clearance of 23.81122 L/h.

Conclusion: These findings contribute to the understanding of AMB-FUBINACA's pharmacokinetics and pharmacodynamics.

Keywords: AMB-FUBINACA; Blood; GC/MS/MS; Pharmacokinetic; Rat.