Finasteride Quantification in Human Plasma by High-Performance Liquid Chromatography Coupled to Electrospray Ionization Tandem Mass Spectrometry. Application to a Comparative Pharmacokinetics Study

Abstract

A specific, fast and sensitive LC-MS/MS assay was developed for the determination of finasteride in human plasma using betamethsone dipropionate as the internal standard (IS). The limit of quantification was 1.0 ng/ml and the method was linear in the range of 1.0-25.0 ng/ml. The retention times were 0.75 min for finasteride and 0.85 min for IS. Method intra-batch precision and accuracy ranged from 3.6 to 7.1%, and 96.6 to 103.9%, respectively. Inter-batch precision ranged from 2.5 to 3.4%, while Inter-batch accuracy ranged from 100.3 to 103.5%. The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of 2 different pharmaceutical formulations containing 1.0 mg of finasteride. This study evaluated 38 volunteers in a randomized, 2-period crossover study with 7 days washout period between doses. The geometric mean and respective 90% CI of finasteride test/reference percent ratios were 95.68% (91.2 - 104.6%) for Cmax, 97.5% (92.1-103.3%) for AUC0-t and 98.1 (92.67-103.8) for AUC0-inf. Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for Cmax and AUC0-inf, it was concluded that the test formulation is bioequivalent to the reference one with respect to the rate and extent of absorption of finasteride.

Use of a monolithic column for the development and validation of a HPLC method for the determination of famotidine, cimetidine and nizatidine in biological fluids

“…A literature survey retrieved a large number of references reporting analytical methods for the determination of these compounds. Mainly separation techniques such as Gas Chromatography (GC) [2], High Performance Thin Layer Chromatography (HPTLC) [3][4][5][6][7][8][9][10], Capillary Electrophoresis (CE) [11][12][13][14][15][16][17] and High Performance Liquid Chromatography (HPLC) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] have been used, with the latter being the predominant technique for the determination of these compounds in a variety of matrices, utilizing different methods of sample pretreatment and detection modes. HPLC with ultra-violet (UV) detection, employing reversed phase particle packed columns, is most frequently used for the analysis of these drugs in pharmaceutical preparations and biological fluids.…”