Comprehensive Bioequivalence Analysis of Naproxen ۵۰۰ mg in Human Plasma Using Advanced LC-MS/MS Techniques

This study presents a detailed bioequivalence analysis of naproxen ۵۰۰ mg tablets through liquid chromatography-tandem mass spectrometry (LC-MS/MS) in human plasma samples. The methodology adhered to EMEA and ICH M۱۵ guidelines, focusing on specificity, carry-over effects, lower limit of quantification (LLOQ), calibration curve linearity, precision, accuracy, matrix effects, and stability. Calibration was established over a concentration range of ۵.۵–۲۶ ppm, yielding robust linearity (R > ۵.۲۲). Analytical validation indicated LLOQ as ۵.۵ ppb, with a signal-to-noise ratio exceeding ۱۵, ensuring sensitivity for bioequivalence assessment. Precision and accuracy were evaluated for intra-day and inter-day variability across low, medium, and high QC levels, achieving relative standard deviations (RSDs) within acceptable limits (< ۱۵%). Stability testing, including freeze-thaw, short-term, and long-term conditions, confirmed method reliability. Matrix effect evaluations demonstrated minimal interference, with extraction recovery exceeding ۲۵%. Pharmacokinetic profiling revealed key metrics such as Cmax and Tmax, confirming bioequivalence between test and reference formulations. The results validate the robustness and applicability of the proposed LC-MS/MS method for bioequivalence studies, contributing to high-throughput analytical workflows in pharmaceutical research.

کلیدواژه ها:

Naproxen ، LC-MS/MS ، bioequivalence ، human plasma ، analytical method validation ، pharmacokinetics ، EMEA guidelines ، ICH M۰۵ ، calibration ، stability