Isolation and characterization of novel degradation products of Doxofylline using HPLC, FTIR, LCMS and NMR.
Forced degradation of Doxofylline (DFL) in different stress (base and peroxide) conditions gave rise to two potential unknown impurities. These unknown degradation products DFL DEG-I and DFL DEG-II were evaluated using a new-reverse-phase high performance liquid chromatography (HPLC), where it was eluted at 0.44 and 1.09 relative retention times to DFL peak. DFL DEG-I and DFL DEG-II were isolated using preparative HPLC from degradation mixtures. The structure of DFL DEG-I and DFL DEG-II were elucidated using high resolution MS, multi-dimensional NMR and FTIR spectroscopic techniques, and characterized. The stereochemistry of the enantiomers in DFL DEG-II has further been investigated using computational techniques. To the best of our knowledge, DFL DEG-I and DFL DEG-II are novel impurities and not reported elsewhere.
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Ch Krishnam
CK
Raju
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Avadhesh K
AK
Pandey
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Gururaj
G
S
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Kaushik
K
Ghosh
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Arunima
A
Pola
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India. Electronic address: skg@usp.org.
Sanath Kumar
SK
Goud P
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Mrunal A
MA
Jaywant
Analytical Research and Development, United States Pharmacopeial Convention - India (P) Ltd., Plot No. D6 & D8, IKP, Genome Valley, Shameerpet, Hyderabad-500078, India.
Sameer G
SG
Navalgund
D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D013806:Theophylline / Q000031:analogs & derivatives* / Q000032:analysis
D013806:Theophylline; C029797:doxofylline
Computational chemistry; HRMS; LC; NMR; Novel impurities of doxofylline