Bioequivalence Study of Finasteride: Analytical Method Validation and Pharmacokinetic Evaluation in Human Plasma

چکیده

This study presents the analytical method validation and pharmacokinetic evaluation of finasteride in human plasma, conducted as part of a bioequivalence assessment. Utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI), the method achieves high sensitivity and specificity for quantifying finasteride at concentrations ranging from 1 to 160 parts per billion (ppb). Method validation adhered to International Council for Harmonisation (ICH) M10 guidelines, covering specificity, precision, accuracy, carry-over, and stability. Key findings include the lower limit of quantification (LLOQ) established at 1 ppb with a signal-to-noise ratio exceeding 10, ensuring robust detection in pharmacokinetic studies.

The pharmacokinetic profile was assessed in 25 volunteers under fasting conditions, using both test and reference formulations of finasteride. Plasma concentrations were measured over a 24-hour period, revealing comparable absorption, distribution, and elimination phases. Statistical analysis confirmed the bioequivalence of the formulations, with key pharmacokinetic parameters—area under the curve (AUC) and maximum plasma concentration (Cmax)—falling within the regulatory acceptance range of 80–125%. Additionally, the stability of finasteride under various conditions, including short-term, freeze-thaw, and long-term storage, demonstrated minimal degradation, reinforcing the reliability of the method for extended studies.

This study underscores the importance of rigorous analytical validation and comprehensive pharmacokinetic evaluation in bioequivalence trials. The validated LC-MS/MS method provides a robust framework for future research on finasteride and similar compounds, ensuring accuracy and reliability in regulatory submissions.