Identification of low-level degradants from low dose tablets.
A multifaceted approach was successfully used to identify three of four unknown degradants in degraded low dose tablets. Accelerated solvent extraction (ASE) was found to be an invaluable tool in this multifaceted approach. ASE was capable of extracting four individual degradants of an active pharmaceutical component from 10 tablets into 15 mL of solvent with approximately 100% recovery for each degradant. Using ASE instead of manual extraction led to the extraction and isolation of the degradants in 1 day instead of 7 days. One of the degradants was extracted by ASE, isolated by semi-prep HPLC, and identified by LC-MS and NMR spectroscopy. The structures of two of the remaining three degradants were confirmed by synthesis of authentic samples, while the fourth degradant is yet to be identified.
Blanchard
Andrew
A
Analytical Research and Development, Pfizer Global Research and Development, Eastern Pt. Road, Groton, CT 06340, USA.
Lee
Carlos
C
Nickerson
Beverly
B
Lohr
Linda L
LL
Jensen
Andrew J
AJ
Alsante
Karen M
KM
Sharp
Thomas R
TR
Santafianos
Dinos P
DP
Morris
Ronald
R
Snyder
Kimberly D
KD
D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D004355:Drug Stability; D006813:Humidity; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D012997:Solvents; D013607:Tablets / Q000032:analysis*; D013696:Temperature
D007202:Indicators and Reagents; D012997:Solvents; D013607:Tablets