Validated specific HPLC methods for determination of prazosin, terazosin and doxazosin in the presence of degradation products formed under ICH-recommended stress conditions.

The present paper describes development of stability-indicating high-performance liquid chromatographic (HPLC) assay methods for three alpha-adrenergic-blocker drug substances, namely, prazosin, terazosin and doxazosin, in the presence of degradation products generated from forced decomposition studies. Resolution of drugs from degradation products was obtained using a reversed-phase C-18 column using water/acetonitrile/methanol/glacial acetic acid/diethylamine (25:35:40:1:0.017) as mobile phase for prazosin and terazosin and acetonitrile/water/glacial acetic acid/diethylamine (65:35:1:0.02) for doxazosin. The detection was done at 254 nm. The methods were validated with respect to linearity, precision, accuracy, specificity and robustness.

The ICH guidance in practice: stress decomposition studies on three piperazinyl quinazoline adrenergic receptor-blocking agents and comparison of their degradation behaviour.

Stress degradation studies were carried out on three piperazinyl quinazoline alpha(1)-adrenergic receptor blockers, viz. prazosin, terazosin, and doxazosin, following the conditions prescribed in the parent drug stability testing guideline (Q1AR) issued by International Conference on Harmonization (ICH). All drugs showed significant decomposition at 80 degrees C in acidic conditions (0.1 M HCl) and complete degradation in alkaline conditions (0.1 M NaOH). Under both these conditions, 2-piperazinyl-6,7-dimethoxy-4-aminoquinazoline was formed as a major decomposition product in all three drugs. The degradation pattern under ICH-prescribed photolytic conditions in liquid and solid states was also similar for all the drugs. The light exposure resulted in the formation of a cluster of degradation products. No degradation was observed in neutral and oxidative conditions. In solid state, all drugs were stable at 50 degrees C in a 1-month study. In alkaline conditions, the order of sensitivity to degradation of the three drugs was doxazosin>terazosin>prazosin, while the same was terazosin>doxazosin>prazosin under acidic conditions. Mechanistic explanation is provided for the variable behaviour of decomposition.