Profiling impurities and degradants of butorphanol tartrate using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry substructural techniques.
A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of butorphanol, the active ingredient in stadol NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structures of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of butorphanol tartrate included oxidative products proposed as 9-hydroxy-and 9-keto-butorphanol, norbutorphanol, a ring-contraction degradant, and delta 1, 10 a-butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnostic tool for new degradation products.
Volk
K J
KJ
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA.
Klohr
S E
SE
Rourick
R A
RA
Kerns
E H
EH
Lee
M S
MS
D000280:Administration, Inhalation; D000701:Analgesics, Opioid / Q000032:analysis*; D002077:Butorphanol / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D013058:Mass Spectrometry / Q000379:methods
D000701:Analgesics, Opioid; D002077:Butorphanol