I. Niopas et Ac. Daftsios, Determination of 2-hydroxyflutamide in human plasma by high-performance liquid chromatography and its application to pharmacokinetic studies, J CHROMAT B, 759(1), 2001, pp. 179-183
dFlutamide is a potent antiandrogen used for the treatment of prostatic can
cer. Flutamide undergoes extensive first-pass metabolism to the pharmacolog
ically active metabolite 2-hydroxyflutamide. A simple, sensitive, precise,
accurate and specific HPLC method, using carbamazepine as the internal stan
dard, for the determination of 2-hydroxyflutamide in human plasma was devel
oped and validated. After addition of the internal standard, the analytes w
ere isolated from human plasma by liquid-liquid extraction. The method was
linear in the 25 to 1000 ng/ml concentration range (r>0.999). Recovery for
2-hydroxyflutamide was greater than 91.4% and for internal standard was 93.
6%. The limit of quantitation was 25 ng/ml. Inter-batch precision, expresse
d as the relative standard deviation (RSD), ranged from 4.3 to 7.9%, and ac
curacy was better than 93.9%. Analysis of 2-hydroxyflutamide concentrations
in plasma samples from 16 healthy volunteers following oral administration
of 250 mg of flutamide provided the following pharmacokinetic data (mean /- SD): C-max, 776 +/- 400 ng/ml; AUC(0-infinity), 5368 +/- 2689 ng h/ml; A
UC(0-t), 5005 +/- 2605 ng h/ml; T-max, 2.6 +/-1.6 h; elimination half-life,
5.2 +/-2.0 h. (C) 2001 Elsevier Science B.V. All rights reserved.