Isolation and characterization of acid and base degradation products in Atenolol and Hydrochlorothiazide and a validated selective stability-indicating HPLCUV method for their quantification

Abstract

Atenolol (( RS )-2-{4-[2-Hydroxy-3-(propan-2-ylamino)propoxy]phenyl}acetamide) and Hydrochlorothiazide (6-chloro-1,1-dioxo-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide) are beta 1 (? 1 ) receptor blocker and diuretic drug respectively; however the combination dosage regime are used for cardiovascular therapy. Thus a forced degradation study was carried out upon this combination drug regime under acidic and basic environment in order to deconvolute the possible degradation product under specified stressed conditions. Under acidic conditions atenolol and hydrochlorothiazide were cleaved into 2-(4-(3-amino-2- oxopropoxy) phenyl) acetamide and 6-sulphamido benzothiazide. However, under basic conditions, the drugs were spliced into 2-(4-(2-hydroxypropoxy) phenyl) acetamide and 2-chloro 4-amino 1, 6-dihydro benzene sulphonamide respectively. The degradant peaks were elucidated by HPLC using C18 column with methanol: phosphate buffer (70:30 v/v) with a flow rate of 0.5ml/min (UV detection at 226nm).. For quantitative method validation, linearity was observed over product concentration range 2g/ml - 100 g/ml (r 2 0.9992) with regression equation y=43432x. The products were first identified by LC-MS and further confirmed by FT-IR and 1 H 1 NMR. A specific and sensitive stability-indicating assay method for the simultaneous determination of the drugs, its process related impurities and degradation products was developed.