Comprehensive Bioequivalence Analysis of Naproxen 500 mg in Human Plasma Using Advanced LC-MS/MS Techniques
کلمات کلیدی:
Naproxen, LC-MS/MS, bioequivalence, human plasma, analytical method validation, pharmacokinetics, EMEA guidelines, ICH M10, calibrationچکیده
This study presents a detailed bioequivalence analysis of naproxen 500 mg tablets through liquid chromatography-tandem mass spectrometry (LC-MS/MS) in human plasma samples. The methodology adhered to EMEA and ICH M10 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 0.5–96 ppm, yielding robust linearity (R² > 0.99). Analytical validation indicated LLOQ as 0.5 ppb, with a signal-to-noise ratio exceeding 10, 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 (<15%). Stability testing, including freeze-thaw, short-term, and long-term conditions, confirmed method reliability. Matrix effect evaluations demonstrated minimal interference, with extraction recovery exceeding 95%. 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.
دانلودها
مراجع
1. Gopinath, C. et al. (2013). Validation of a high-throughput LC-MS/MS method for simultaneous determination of esomeprazole and naproxen in human plasma. *Biomedical Chromatography*. 27(7). 932-939.
2. European Medicines Agency (EMA). (2012). Guideline on bioanalytical method validation. *EMA/CHMP/EWP/192217/2009 Rev. 1 Corr.* European Medicines Agency.
3. International Council for Harmonisation (ICH). (2021). M10: Bioanalytical Method Validation. ICH Harmonised Guideline.
4. Shen, X. et al. (2020). Advances in LC-MS/MS technologies for bioequivalence studies: Applications to NSAIDs. *Analytical and Bioanalytical Chemistry*. 412(2). 249-266.
5. Wang, R. et al. (2021). Matrix effects in LC-MS/MS bioanalysis and its impact on pharmacokinetic studies. *Journal of Analytical Science and Technology*. 12(5). 55-67.
6. Zhang, H. and Liu, M. (2020). Solid-phase extraction techniques for plasma sample preparation in bioanalytical LC-MS/MS: A comprehensive review. *Trends in Analytical Chemistry*. 124. 115762.
7. Singh, J. and Jain, M. (2022). Applications of LC-MS/MS in personalized medicine: Monitoring NSAID bioavailability. *Journal of Pharmaceutical Analysis*. 12(4). 501-513.
