Isolation and characterization of impurities in docetaxel.
During the process development of docetaxel, two polar impurities (Impurities I and II) and two non-polar impurities (Impurities III and IV) were detected by high performance liquid chromatography (HPLC). All the impurities were isolated by Medium Pressure Liquid Chromatography (MPLC). The Impurities I, II, III and IV were identified as 13-[(4S,5R)-2-oxo-4-phenyl-oxazolidine-5-carboxy]-10-deacetyl baccatin III ester, 2'-epi docetaxel, 7-epi docetaxel and 13-[(4S,5R)-2-oxo-4-phenyl-oxazolidine-3,5-dicarboxyl-3-tert-butyl)]-10-deacetyl baccatin III ester, respectively, based on one- (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy data. The Impurity IV was crystallized and the structure was solved by single crystal X-ray diffraction (XRD). Two impurities (Impurities II and III) were found to be process related, while the remaining two impurities (Impurities I and IV) turned out to be isomers. The formation of these impurities was discussed.
Vasu Dev
R
R
Department of Analytical Research, Discovery Research, Dr. Reddy's Laboratories Ltd., Bollaram Road, Miyapur, Hyderabad 500049, Andhra Pradesh, India.
Moses Babu
J
J
Vyas
K
K
Sai Ram
P
P
Ramachandra
P
P
Sekhar
N M
NM
Mohan Reddy
D N
DN
Srinivasa Rao
N
N
D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D043823:Taxoids / Q000032:analysis*
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel