Related Compounds: Atorvastatin Calcium

SILVIA GABRIELA FORAY; ANA JULIETA PEPINO, MARTÍN SEBASTIÁN FAILLACE, WALTER JOSÉ PELÁEZ, GUSTAVO ALEJANDRO ARGÜELLO

Córodba

Congreso; 3ra Reunión Internacional de Ciencias Farmacéuticas; 2014

Universidad Nacional de Córdoba

Standards related compounds are routinely used for quality assesment of raw materials of active pharmaceutical ingredients (APIs). They are very expensive and are sold by a few miligrams by United States Pharmacopoeia (USP). According to USP Atorvastatin Calcium has several related compounds (RC): desfluoro (related compound A); 3S,5R isomer (B); difluoro (C); epoxide (D); 3S,5S enantiomer (E); diamino; 3-deoxyhept-2-enoic acid; lactone (H); epoxide tetrahydrofuran analog; ethyl ester and acetonide (I). These compounds have an acceptance criteria no more than (NMT) 0,1-0,3% and other minor impurities (NMT 0,1%) depending on the synthetic route. The aim of this work was obtain by synthesis or degradation of Atorvastatin calcium working standards of related compounds for quality control. We have synthetized lactona (related compound H), α,β-unsaturated lactone, methyl ester of Atorvastatin and Atorvastatin acid. Lactone is a synthetic precursor of calcium salt, and therefore is an impurity of synthesis and a degradation product of Atorvastatin calcium, as it is easily formed in weakly acidic media. Atorvastatin methyl ester is a synthetic impurity. The α,β-unsaturated lactone, is a impurity of acidic degradation. These compounds were purified by column chromatography and recristalization. They were characterized by NMR (1H-NMR, 13C-NMR, and homo and heteronuclear correlation spectroscopy), FTIR and HPLC. Bruker NMR (200MHz) spectrometer, Shimadzu FTIR, Waters HPLC were used. Lactone was succesfully obtained with a good yield, purified, identified and used as working standard for quality control. The methyl ester compound was characterized but it was not the major product of the synthesis. The α,β-unsaturated lactone was obtained in drastic acidic condition, where both lactone isomers were formed. Atorvastatin acid were also identified by NMR and FTIR. We concluded that it is possible to obtain some Atorvastatin impurities in laboratory by simple and low expensive procedures.