TY - JOUR
T1 - Characterization of process-related impurities including forced degradation products of alogliptin benzoate and the development of the corresponding reversed-phase high-performance liquid chromatography method
AU - Zhou, Yuxia
AU - Zhou, Wentao
AU - Sun, Lili
AU - Zou, Qiaogen
AU - Wei, Ping
AU - Ouyang, Pingkai
PY - 2014/6
Y1 - 2014/6
N2 - The characterization of process-related impurities and forced degradants of alogliptin benzoate (Alb) in bulk drugs and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Alb was found to be unstable under acid and alkali stress conditions and two major degradation products (Imp-F and Imp-G) were observed. The optimum separation was achieved on Kromasil C18 (250 × 4.6 mm, 5 μm) using 0.1% perchloric acid (pH adjusted to 3.0 with triethylamine) and acetonitrile as a mobile phase in gradient mode. The proposed method was found to be stability indicating, precise, linear (0.10-75.0 μg/mL), accurate, sensitive, and robust for the quantitation of Alb and its process-related substances and degradation products. The structures of 11 impurities were characterized and confirmed by NMR spectroscopy, MS, and IR spectroscopy, and the most probable formation mechanisms of all impurities were proposed according to the synthesis route.
AB - The characterization of process-related impurities and forced degradants of alogliptin benzoate (Alb) in bulk drugs and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Alb was found to be unstable under acid and alkali stress conditions and two major degradation products (Imp-F and Imp-G) were observed. The optimum separation was achieved on Kromasil C18 (250 × 4.6 mm, 5 μm) using 0.1% perchloric acid (pH adjusted to 3.0 with triethylamine) and acetonitrile as a mobile phase in gradient mode. The proposed method was found to be stability indicating, precise, linear (0.10-75.0 μg/mL), accurate, sensitive, and robust for the quantitation of Alb and its process-related substances and degradation products. The structures of 11 impurities were characterized and confirmed by NMR spectroscopy, MS, and IR spectroscopy, and the most probable formation mechanisms of all impurities were proposed according to the synthesis route.
KW - Alogliptin benzoate
KW - Forced degradation
KW - Process-related impurities
KW - Quantification
KW - Structural elucidation
UR - http://www.scopus.com/inward/record.url?scp=84902089990&partnerID=8YFLogxK
U2 - 10.1002/jssc.201301384
DO - 10.1002/jssc.201301384
M3 - 文章
C2 - 24616424
AN - SCOPUS:84902089990
SN - 1615-9306
VL - 37
SP - 1248
EP - 1255
JO - Journal of Separation Science
JF - Journal of Separation Science
IS - 11
ER -