Development and validation of an HPLC method for pentazocine quantification: Insights into pharmacokinetics using...

High-Performance Liquid Chromatography (HPLC) has been employed as an analytical procedure for the quantitative analysis of drugs in pharmaceutical and biological samples, owing to its higher sensitivity, accuracy, and reproducibility. In pharmacokinetic analysis, accurate analytical procedures are needed to quantify the concentration of drugs, especially when new delivery systems are used. Biodegradable polymeric nanoparticles have been used as carriers for drugs because they can increase the stability, control the release and improve the bioavailability of drugs.

The objectives of the study was the development/modification of a performance liquid chromatographic method and its validation before it was applied to profiling the pharmacokinetic behavior of the developed biodegradable polymeric nanoparticles.

Pentazocine-loaded biodegradable polymeric nanoparticles were prepared using chitosan-STPP (CP-2) via ionic gelation and Poly (lactic-co-glycolic acid) (JB5) via emulsion solvent evaporation. The method, adapted from reported protocols, was optimized for laboratory conditions and validated according to ICH Q2(R1) guidelines. Validation parameters included linearity, precision, accuracy, working range, limit of detection (LOD) and limit of quantification (LOQ).

The method demonstrated excellent linearity (10-1000ng/mL, R² = 0.9983), precision (%RSD <2%), accuracy (98-102%), LOD of 3.3ng/mL and LOQ of 10ng/ml. In vivo pharmacokinetic studies were performed in 12 healthy male rabbits divided into control and two test groups (n=4 per group). The test groups received nanoparticle formulations, while the control received pentazocine solution. Both nanoparticle formulations showed higher C_max (185.26 and 193.71 ng/mL) and prolonged half-life (9.50 and 8.58 h) compared to control (101.49 ng/mL; 1.69 h). Area under the curve AUC_₀-∞ values were markedly increased for CP-2 and JB5, indicating enhanced bioavailability.

The validated method is suitable for pharmacokinetic profiling and results demonstrate the potential of biodegradable nanoparticles to improve pentazocine delivery.