| DOI: https://doi.org/10.29090/psa.2018.02.077 | Pharm Sci Asia 2018; 45(2), 77-92 |
Synthesis and content determination of impurity A of terazosin for use to establish a reference standard for terazosin drug quality control D.T. Thanh-Thuy, T.X. Nguyen, H.N. Nguyen, C.S. Doan
1 Department of Pharmaceutical Chemistry, Hanoi University of Pharmacy, Hanoi, Vietnam
2 National Institute of Drug Quality Control, Hanoi, Vietnam
Terazosin, a quinazoline derivative is an alpha-1-selective adrenoceptor blocking agent commontly used for the treatment of symptomatic benign prostatic hyperplasia. To control quality of material and finished products of terazosin it is required to have some terazosin related compound reference standards including impurity A of terazosin (IAT). This study aims include the synthesis of IAT to establish a reference standard for drug quality control and investigation of an HPLC method to determine the content of the obtained IAT. The chemicals for synthesis and analysis were purchased from Sigma Aldrich and Merck (Germany). IAT was synthesized from 2-chloro-6,7-dimethoxyquinazoline-4-amino and piperazine, using isoamyl alcohol as a solvent. IAT’s purification was carried out by column chromatography. Spectroscopic methods including IR, MS, NMR were used to characterize and confirm the structure of the product. The HPLC method, which was investigated to determine the content of IAT was validated according to the ICH guidelines. The total yield of synthesis and purify process of IAT was 71.1%. The content of of the purified IAT was determined by comparison to USP Terazosin Related Compound A RS and its content achieved 97.28% calculated on the basis (99.41% calculated on the dried basis). Our results proposed the new synthesis, purification procedures for IAT and the determination method for the content of this product. The IAT obtained can be used to establish a reference standard substance for terazosin drug quality control.
Keyword:
Impurity A, terazosin, synthesis, terazosin related compound A
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