PRE CLINICAL PHARMACOKINETICS OF ALFUZOSIN FORMULATIONS IN RABBITS BY HP LC

The objective of the current study was the pre - clinical evaluation of alfuzosin in rabbits . A simple , specific and simple HPLC method has been developed for estimation of Alfuzosin with 10 0 µL of rabb it plasma using Doxazosin as an internal standard (IS). The Waters HPLC with PDA detector at 245 nm . A s imple protein precipitation extraction process with acetonitrile was used to extract Alfuzosin and IS ( Doxazosin ) from rabbit plasma. The total run tim e was 3.00 min and the elution of Alfuzosin and Doxazosin occurred at 1.49 min and 2.14 min , this was achieved with a m obile phase consisting of buffer : acetonitrile ( 6 0 : 4 0, v/v) at a flow rate of 0.80 mL/min on a Inertsil C 8 ( 1 50 x 4.6 mm, 5 µm) column . Buffer was prepared by mixing 0.02 M potassium dihydrogen orthophosphate and 1mL triethyl amine in 1000 mL and it was adjusted to (pH - 3.5) with ortho phosphoric acid. The developed method was validated in rabbit plasma with a lower limit of quantitatio n of 0.05 µ g/mL for Alfuzosin . A linear response function was established for the range of concentrations 0.05 to 5 .0 µ g/mL ( r > 0.998 ) for Alfuzosin . The intra and inter - day precision values for Alfuzosin met the acceptance criteria as per FDA guidelines . Alfuzosin was stable in a set of stability studies viz., bench - top, auto - sampler and freeze/thaw cycles. This method is free from interference from the plasma blank or solvents used during the optimization. The current f ast track assay method was success fully applied for the oral pharmacokinetic stud ies of 1 0 mg extended release tablets of Alfuzosin Hydrochloride and its in vivo evaluation with reference formulations.