Synthesis and content determination of impurity A of terazosin for use to establish a reference standard for terazosin drug quality control

Terazosin hydrochloride (1-(4-Amino6,7-dimethoxy-2-quinazolinyl)-4-(tetrahydro-2furoyl) piperazine monohydrochloride), (Figure 1), a quinazoline derivative is an alpha-1-selective adrenoceptor blocking agent. It is a highly selective potent α1 adreno-receptor antagonist, an effective drug for hypertension by relaxing veins and arteries, and for the symptomatic treatment of urinary obstruction caused by benign prostatic hyperplasia (BPH) by relaxing the muscles of the bladder and prostate. It is common that a patient with symptomatic BPH also has hypertension. So terazosin is often a convenient choice for these kind of patients to target both diseases1-3. Currently terazosin is being marketed in Asean and many countries in the world with many trade names such as Hytrin, Teraz, Apo-Terazosin, Teradip, Terazosabb, Terazosine EG and Terazosine Sandoz. To control the quality of material and finished products of terazosin, it is required to have some terazosin related compound reference standards including