A multidisciplinary approach to identify a degradation product in a pharmaceutical dosage form.
An unknown degradation product found in non-MS compatible HPLC analysis was studied using a multidisciplinary approach. The unknown was separated and isolated from other components in the drug product by HPLC followed by ion trap MS to obtain MS(n) fragmentation patterns. Its chemical formula was determined using a high resolution time-of-flight mass spectrometer (TOF MS). Nuclear Magnetic Resonance (NMR) was used to elucidate the molecular structure. The impurity was identified as 5-hydroxymethyl furfural, which was a degradation product of lactose, one of the excipients used in the formulation of this dosage form.
Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. charles.pan@novartis.com
Changkang
C
Pan
Jack
J
Guan
Melissa
M
Lin
D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D006868:Hydrolysis; D007785:Lactose / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008832:Microchemistry / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical
D005079:Excipients; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D007785:Lactose