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Determination of flutamide and hydroxyflutamide in dog plasma by a sensitive high performance liquid chromatography method utilizing mid‐bore chromatography
Author(s) -
Farthing Don,
Sica Domenic,
Fakhry Itaf,
Walters Denise Lowe,
Cefali Eugenio A.,
Allan Geoffrey
Publication year - 1994
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1130080511
Subject(s) - commonwealth , clinical pharmacology , medicine , library science , history , pharmacology , archaeology , computer science
Flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyllpropanamide) is a nonsteroidal antiandrogen employed in the management of prostatic carcinoma. Metabolic studies have demonstrated that flutamide is rapidly and extensively metabolized. The major plasma metabolite with pharmacological activity equal to or greater than flutamide is hydroxyflutamide. Variability in the bioavailability of flutamide has been reported (Radwanski et af. , 1989); in order to study the influence of several dosage forms on overall absorption, an assay for the determination of flutamide and hydroxyflutamide in plasma was developed. Several methods for the determination of flutamide and hydroxyflutamide have been previously reported. These methods were characterized by a variety of limiting features such as cumbersome and costly liquidliquid extractions (Belanger el af., 1988; Schulz et af., 1988; Asade et af., 1991), complex detection equipment employing radioactivity and electron capture detection (Radwanski et af., 1989; Schulz et af., 1988), a large sample volume (2 mL) (Asade et af., 1991) or were not utilized for determination in biological samples (Snycerski, 1989). Accordingly, we have developed a simple and sensitive procedure which can be employed in the analysis of flutamide and hydroxyflutamide . The method described demonstrates a cost-effective means of determining both components while maintaining excellent sensitivity and resolution. The utilization of mid-bore chromatography increases the method sensitivity while simultaneously conserving on the quantities of mobile phase required for analysis and subsequent disposal of as hazardous waste. A formal extraction process is not required for this process and the accuracy and precision of this method precludes the need for an internal standard. The sensitivity achieved with this method is excellent using ultraviolet (UV) detection and a sample volume of 150pL of plasma.