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.
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| 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.
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| Authors | A Guarna, G Danza, G Bartolucci, A Marrucci, S Dini, M Serio |
| Journal | Journal of chromatography. B, Biomedical applications (J Chromatogr B Biomed Appl) Vol. 674 Issue 2 Pg. 197-204 (Dec 15 1995) ISSN: 1572-6495 [Print] Netherlands |
| PMID | 8788149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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