Finasteride Quantification in Human Plasma by High-Performance Liquid Chromatography Coupled to Electrospray Ionization Tandem Mass Spectrometry. Application to a Comparative Pharmacokinetics Study.
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.
Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos, Campinas, SP, Brazil.
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Moreno
Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos, Campinas, SP, Brazil.
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Moreno
Faculdade de Medicina da Santa Casa de São Paulo, São Paulo/SP, Brazil.
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Borges
Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos, Campinas, SP, Brazil.
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Donato
Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos, Campinas, SP, Brazil.
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Oliveira
Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos, Campinas, SP, Brazil.
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NC
Borges
D058891:5-alpha Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D001623:Betamethasone / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D018120:Finasteride / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
D058891:5-alpha Reductase Inhibitors; D018120:Finasteride; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone