A new reverse-phase high performance liquid chromatographic method for determination of flutamide in liposomes, rat blood plasma and tablet dosage forms
Keywords:
Flutamide, Reverse-Phase High Performance Liquid ChromatographyAbstract
Flutamide is an anti-androgen widely used in treatment of prostate cancer by affecting Prostate SpecificAntigen (PSA) level in blood, which requires its stability in blood for enough time. A new pharmaceuticaldosage form, liposomes, has been developed for improving efficacy of this drug. The aim of this studyis to develop HPLC UV method for the determination of FLT in liposomes, rat blood plasma and different marketed tablet dosage forms. The method involved less time-consuming sample preparationsteps. The internal standard (IS) for the assay procedure was 6-Mercaptopurine. The samples wereinjected on to reverse-phase (Thermosil® C18) column. The mobile phase, Methanol: Water (80:20, v/v)was run at a flow rate of 1 ml/min for 8 min. The FLT was detected by UV detector at 295 nmwavelength. The retention times for IS and FLT were 3.03 and 4.02 min, respectively. The method waslinear over the concentration range 20-1000 ng/ml and 50-1000 μg/ml in mobile phase and rat bloodplasma, respectively. The method was validated for accuracy, precision, robustness and recovery. Thelimit of detection was 0.099μg/ml and 0.106μg/ml in mobile phase and rat blood plasma, respectively.The method was shown to be highly reproducible and it seems to be adequate for routine therapeuticdrug monitoring. It could be used without any interference from lipids, tablet excipients and endogenoussubstances from the plasma samples.Downloads
References
Goldspiel BR, Kholer DR, Flutamide: an antiandrogen for advanced prostate cancer. Drug Intelligence and Clinical Pharmacy 1990; 24: 611-623.
Berson A., Wolf C., Chachaty C., Metabolic activation of the nitro aromatic antiandrogen flutamide by rat and human cytochromes P-450, including forms belonging to the 3A and 1A subfamilies J.Pharmacol.Exp.Ther. 1993; 265: 366-372.
Schulz M., Schmoldt A., Donn F., Becker H., The pharmacokinetics of flutamide and its major metabolites after a single oral dose and during chronic treatment. Eur.J.Clinical. Pharmacol. 1988; 34: 633-636.
Brogden R., Clissold S., Flutamide: A preliminary review of its pharmacodynamic and pharmacokinetics properties, and its therapeutic efficacy in advanced prostate cancer. Drugs 1989; 38:185-203.
Aso Y., Akaza H., Koiso K., Kumamoto Y., Hawai T., Origasa S., Hinyokika Kiyo 1993; 39: 381-389.
Chabner BA, Allegra CJ, Curt CA, Calabresi P., in: A. Goodman, J.G. Hardman, L.E. Limbird, P.B. Milinoff, R.W. Ruddan (Eds.), The Pharmacological Basis of Therapeutics, 9th ed., Mc-Graw Hill, Mexico, 1996, pp. 1309-1367.
Squella JA, Pena C., Alvarez-Lueje A., Electrochemical Study of Flutamide, an Anticancer Drug, and Its Polarographic, UV Spectrophotometric and HPLC Determination in Tablets. Electroanalysis 1998;10(15): 1043-51.
Miranda A, Caraballo I, Millan M., Stability study of flutamide in solid state and in aqueous solution. Drug Dev. Ind. Pharm. 2002; 28(4): 413 – 422.
Campanero MA, Sacaba B, Garcia-Quelglas E, Development of a sensitive method for the determination of ganciclovir by reversed-phase high-performance liquid chromatography J.Chromatogr.B 1998; 706: 311-317.
Zhong Z, Yum KT, Diakur J, Hydroxypropyl-β-cyclodextrin flutamide inclusion complex II: Oral and intravenous
pharmacokinetics in rats. J.Pharm.Pharmaceut.Sci, 2002; 5(3): 292-298.
Bangham AD, Standish MM, Watkins JC, Preparation of multilamellar vesicles of defined size-distribution by solventspherule evaporation. J. Mol. Biol. 1965; 13: 238-252.
Betagiri GV, Jenkins SA, Parsons DL, Liposomal Drug Delivery Systems, tenth ed., Technomic Publications, Lancaster, 1993.
Merodia M, Mirshahi T, Mirshahi M, Development of a sensitive method for the determination of ganciclovir by reversedphase
high-performance liquid chromatography J.Chromatogr. 2000; 870: 159-167.
Bhalerao SS, Harshal AR, Preparation, optimization, characterization, and stability studies of salicylic acid. Drug Dev.
Ind. Pharm. 2003; 29(4): 451-467.
Winefordner JD, Long GL, Limit of detection. A closer look at the IUPAC definition. Anal. Chem. 1983; 55: 712A-724A.
ICH Topic Q2B, Pharmaeuropa, 8. 1996; 108-111.
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