Determination of 2-hydroxyflutamide in human plasma by high-performance liquid chromatography and its application to pharmacokinetic studies |
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| Institution: | 1. Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 54006 Thessaloniki, Greece;2. Analyses of Pharmaco-Chemical Products, American Farm School of Thessaloniki, P.O. Box 23, 55102 Thessaloniki, Greece;1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China;2. Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China;3. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;4. Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China;1. Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas (Madrid) 28108, Spain;2. Discovery Chemistry Research and Technologies, Eli Lilly and Company, Indianapolis, IN 46285, United States;1. Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China;2. State Key Lab of CAD&CG, Zhejiang University, Hangzhou, Zhejiang 310058, China;3. Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China;1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China;2. Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Nanjing 210009, China;3. Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China;4. Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China;5. School of Food and Bioengineering, Shaanxi University of Science & Technology, Xi’an 710021, China |
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| Abstract: | 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 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, 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; AUC0–∞, 5368±2689 ng h/ml; AUC0–t, 5005±2605 ng h/ml; Tmax, 2.6±1.6 h; elimination half-life, 5.2±2.0 h. |
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