ABSTRACT:
A rapid, sensitive and specific positive electrospray liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of tamsulosin hydrochloride (TAM) in capsules and tablets was developed and validated. The method was applied for measuring TAM contents in 6 different brands of the drug and for evaluating the in vitro dissolution profiles of those brands under simulated gastric conditions. The MS analysis was performed using MS XTerra® RP-C8 column under isocratic conditions using a mobile phase of acetonitrile: water: formic acid (80:20:50µl v/v/v) at a flow rate of 0.4 ml/min. Quantitative analysis was performed using MRM transitions at m/z 410.4>148.6 (TAM) and m/z 236.8>120.4 (procainamide as IS). The established calibration curves showed good linearity (r: 0.995 ± 0.003) over the concentration range 1-25 µg/ml of TAM with a limit of quantification (LOQ) of 1.0 µg/ml (RSD% < 24.1)and limit of detection of 0.39µg/ml. The intra-day and inter-day precision (RSD%) were <10.8%, whereas the intra-day and inter-day accuracy (Bias%) were < +1.4 %. Content uniformity study using LC-MS/MS indicated that TAM contents were in the range of 0.295-0.379 mg (dose: 0.4 mg). Dissolution studies using LC-MS/MS showed that the % release values of TAM from the controlled-release formulations varied from 4.2 to 53.8%, whereas for immediate-release formulation, the % drug release was 89.2%. Statistical analysis using student-t test indicated significant differences between the reference brand and some generic brands of TAM with respect to content uniformity and dissolution testing. The obtained results proved that the developed LC-MS/MS method was successful for the analysis of low-dose TAM products for both content uniformity and in vitro dissolution studies.