title: Synthesis of 5,6,6-[2H3]finasteride and quantitative determination of finasteride in human plasma at picogram level by an isotope-dilution mass spectrometric method.
abstract: Finasteride is a potent inhibitor of the enzyme steroid 5 alpha-reductase now approved as a drug for the treatment of benign prostatic hyperplasia. We describe an original method for the quantitative determination of finasteride at picogram level in human plasma by isotope-dilution gas chromatography mass spectrometry. 5,6,6-[2H3]Finasteride was synthesized with an high ratio of trideuteration (finasteride/[2H3]finasteride = 0.007) allowing its optimal use as internal standard. Plasma samples were purified in a single-step procedure on solid-phase extraction C18 columns with a recovery > or = 90%. Samples were injected in the GC-MS instrument without any derivatization and the minimum detection level of finasteride was 50 pg with a signal-to-noise ratio of 6:1. The coefficients of variation for the 5 and 10 ng/ml (plasma) concentrations were 5.8% and 4%, respectively. The method has been applied to the determination of the plasma pharmacokinetic of finasteride in five male volunteers treated with a single 5-mg dose of the drug, affording kinetic parameters which are in good agreement with the values previously reported with a different methodology. The present method results accurate, specific, sensible and reliable for a routinely determination of finasteride at picogram levels.
authors.affiliation: Dipartimento di Chimica Organica Ugo Schiff, Università di Firenze, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Guarna
authors.forename: G
authors.initials: G
authors.lastname: Danza
authors.forename: G
authors.initials: G
authors.lastname: Bartolucci
authors.forename: A
authors.initials: A
authors.lastname: Marrucci
authors.forename: S
authors.initials: S
authors.lastname: Dini
authors.forename: M
authors.initials: M
authors.lastname: Serio
mesh_terms: D003903:Deuterium; D004791:Enzyme Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D018120:Finasteride / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007201:Indicator Dilution Techniques; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D008832:Microchemistry
chemical_list: D004791:Enzyme Inhibitors; D018120:Finasteride; D003903:Deuterium