SYNTHESIS OF 5,6,6-[H-2(3)]FINASTERIDE AND QUANTITATIVE-DETERMINATIONOF FINASTERIDE IN HUMAN PLASMA AT PICOGRAM LEVEL BY AN ISOTOPE-DILUTION MASS-SPECTROMETRIC METHOD

Finasteride is a potent inhibitor of the enzyme steroid 5 alpha-reduct ase now approved as a drug for the treatment of benign prostatic hyper plasia. We describe an original method for the quantitative determinat ion of finasteride at picogram level in human plasma by isotope-diluti on gas chromatography mass spectrometry. 5,6,6-[H-2(3)]Finasteride was synthesized with an high ratio of trideuteration (finasteride/[H-2(3) ]finasteride = 0.007) allowing its optimal use as internal standard. P lasma samples were purified in a single-step procedure on solid-phase extraction C-18 columns with a recovery greater than or equal to 90%. Samples were injected in the GC-MS instrument without any derivatizati on and the minimum detection level of finasteride was 50 pg with a sig nal-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 pharmacokin etic of finasteride in five male volunteers treated with a single 5-mg dose of the drug, affording kinetic parameters which are in good agre ement 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.