Determination of 2-hydroxyflutamide in human plasma by high-performance liquid chromatography and its application to pharmacokinetic studies.
Flutamide is a potent antiandrogen used for the treatment of prostatic cancer. Flutamide undergoes extensive first-pass metabolism to the pharmacologically active metabolite 2-hydroxyflutamide. A simple, sensitive, precise, accurate and specific HPLC method, using carbamazepine as the internal standard, for the determination of 2-hydroxyflutamide in human plasma was developed and validated. After addition of the internal standard, the analytes were isolated from human plasma by liquid-liquid extraction. The method was linear in the 25 to 1,000 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, expressed as the relative standard deviation (RSD), ranged from 4.3 to 7.9%, and accuracy 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): Cmax, 776 +/- 400 ng/ml; AUC(0-infinity), 5,368 +/- 2,689 ng h/ml; AUC(0-t) 5,005 +/- 2,605 ng h/ml; Tmax 2.6 +/- 1.6 h; elimination half-life, 5.2 +/- 2.0 h.
Niopas
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Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Greece. niopas@pharm.auth.gr
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D000328:Adult; D000726:Androgen Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000726:Androgen Antagonists; C014290:hydroxyflutamide; D005485:Flutamide