Bioequivalence Study of Finasteride

Abstract

Two different finasteride (CAS 98319-26-7) tablet formulations were evaluated for their relative bioavailability (Flaxin tablets 5 mg, as the test formulation vs reference formulation, tablets 5 mg) in 23 healthy male volunteers who received a single 5 mg oral dose of each preparation. The study was open, randomized with a two-period crossover design and a 7-day washout period. Plasma samples were obtained over a 48-h interval. The finasteride concentrations were determined by high-pressure liquid chromatography (HPLC) coupled to tandem mass spectrometry (LC-MS-MS). The analytical method developed has a limit of quantitation (LOQ) of 0.50 ng/ml in plasma. For the quality control the measured concentration was 2.05 +/- 0.14 ng/ml (mean +/- SD, n = 30) with a precision of 6.9% and an accuracy of 2.55% at a concentration of the starting solution of 2.00 ng/ml, while with 20.00 ng/ml starting solution the measured concentrations were 20 +/- 0.80 ng/ml (n = 30) with a precision of 3.81% and an accuracy of 0.09%. From the plasma finasteride concentration vs time curves the following pharmacokinetics parameters were obtained: AUC0-48, AUC0-infinity, Cmax, Cmax/AUC0-48, Ke, elimination half-life and tmax. Geometric mean test/reference formulations individual percent ratio was 95.71 for AUC0-48 h and 88.70% for Cmax. The 90% confidence interval for the geometric mean of the individual ratio test/reference formulations was 95.70-120.20% for AUC0-48 h, 94.60-121.30 for AUC0-infinity and 88.70-108% for Cmax. Since for both Cmax or AUC the 90% Cl values are within the interval proposed by the Food and Drug Administration, the test formulation is bioequivalent to the reference formulation for both the rate and extent of absorption after single dose administration.

Rapid determination of finasteride in human plasma by UPLC–MS/MS and its application to clinical pharmacokinetic study

“…The pH 3 mobile phase was optimal for both MS sensitivity and chromatographic separation. The UPLC technique, with smaller column particle size (1.7 m), separated finasteride and the IS from the sample matrix within 3 min, significantly faster than previous LC-MS methods [12,[14][15][16].…”

“…The line equation for this calibration curve was y = 0.146x − 0.00607, where y is the peak area ratio of finasteride to the IS and x is the concentration of finasteride in ng/mL. Improved chromatographic efficiency of UPLC gives better sensitivity to the method (0.1 ng/mL) than that of pervious studies using LC-MS [12,[14][15][16][17][18].…”

“…The quantitation of finasteride in biological samples has been performed with several methods including high-performance liquid chromatography (HPLC) [6][7][8], isotope-dilution mass spectrometry [9], polarography [10], spectrophotometry [11], and highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) [12][13][14][15][16][17][18]. Although HPLC is a well-established technique, it suffers from poor sensitivity and specificity.…”

“…Previous methods have involved multistep sample preparations such as solid-phase extraction [8,18] and run times up to 38 min [6]. The addition of tandem MS/MS significantly enhances the sensitivity and specificity [13], but the chromatographic run times are still too long for high-throughput analyses [12,[14][15][16]. Also, one of these methods [16] uses trifluoroacetic acid as mobile phase additive, which is reported to suppress electrospray ionization signals of analyte ions [19].…”

Spectrofluorimetric study of finasteride and bovine serum albumin interaction and its application for quantitative determination of finasteride in tablet dosage form

“…1 Propecia was also approved by the FDA in 1997 for use in males only for the treatment of male pattern hair loss (androgenetic alopecia). [29][30][31][32][33] In the current study, quenching of the intrinsic uorescence of BSA was investigated by selectively exciting BSA. 3 Their interaction with drugs can affect the distribution volume and elimination rate of drugs.…”