Application of LC-MSn in conjunction with mechanism-based stress studies in the elucidation of drug impurity/degradation product structures and degradation pathways

American Pharmaceutical Review

Volumn 11, Issue 1, 2008, Pages

  Li, Min ^a   Chen, Bin ^a   Lin, Mingxiang ^a   Rustum, Abu ^a  

^a Analytical Sciences Schering Plough Corporation

Author keywords

Degradation pathway; Drug degradant; Drug impurity; Forced degradation; LC MS; LC MS MS; Stress study

Indexed keywords

BETAMETHASONE 9,11 EPOXIDE; BETAMETHASONE DIPROPIONATE; DRUG METABOLITE; UNCLASSIFIED DRUG;

ARTICLE; DRUG DEGRADATION; DRUG IMPURITY; DRUG OXIDATION; DRUG STABILITY; GOOD MANUFACTURING PRACTICE; LIQUID CHROMATOGRAPHY; TANDEM MASS SPECTROMETRY;

EID: 55849105969     PISSN: 10998012     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (9)

1. United States Federal Register, Vol. 65, No. 251.
2. ICH Harmonised Tripartite Guideline, Impurities in New Drug Substances, Q3A(R2), Current Step 4 version, dated 25 October 2006.
3. Li, M.; Conrad, B.; Maus, R. G.; Pitzengburger, S. M.; Subramanian, R.; Fang, X.; Kinzer, J. A.; Perpall, H. J. Tetrahedron Lett. 2005, 46, 3533-3536.
4. Lewbart, M. L.; Mattox, V. R. J. Org. Chem. 1963, 28, 1779-1786, and the references cited therein.
5. Li, M.; Chen, B.; Lin, M.; Chan, T.-M.; Fu, X.; Rustum, A. Tetrahedron Lett. 2007, 48, 3901-3905.
6. Our results are consistent with a recent report in that the MS2 spectra of betamethasone and dexamethasone are similar but distinguishable: Arthur, K. E.; Wolff, J.-C.; Carrier, D. J. Rapid Commun. Mass Spectrom. 2004, 18, 678-684.
7. The details related to this topic are summarized in another manuscript of our group, which is to be submitted for publication.
8. Based on our experience, this particular MS detector is prone to the formation of significant solvent adducts.
9. Mattox, V. R. J. Am. Chem. Soc. 1952, 74, 4340-4347.