title: Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine.
abstract: BACKGROUND
  Lumefantrine (benflumetol) is a fluorene derivative belonging to the aryl amino alcohol class of anti-malarial drugs and is commercially available in fixed combination products with β-artemether. Impurity characterization of such drugs, which are widely consumed in tropical countries for malaria control programmes, is of paramount importance. However, until now, no exhaustive impurity profile of lumefantrine has been established, encompassing process-related and degradation impurities in active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs).
  
  
  METHODS
  Using HPLC-DAD/UV-ESI/ion trap/MS, a comprehensive impurity profile was established based upon analysis of market samples as well as stress, accelerated and long-term stability results. In-silico toxicological predictions for these lumefantrine related impurities were made using Toxtree® and Derek®.
  
  
  RESULTS
  Several new impurities are identified, of which the desbenzylketo derivative (DBK) is proposed as a new specified degradant. DBK and the remaining unspecified lumefantrine related impurities are predicted, using Toxtree® and Derek®, to have a toxicity risk comparable to the toxicity risk of the API lumefantrine itself.
  
  
  CONCLUSIONS
  From unstressed, stressed and accelerated stability samples of lumefantrine API and FPPs, nine compounds were detected and characterized to be lumefantrine related impurities. One new lumefantrine related compound, DBK, was identified and characterized as a specified degradation impurity of lumefantrine in real market samples (FPPs). The in-silico toxicological investigation (Toxtree® and Derek®) indicated overall a toxicity risk for lumefantrine related impurities comparable to that of the API lumefantrine itself.
authors.affiliation: Drug Quality and Registration group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Verbeken
authors.forename: Sultan
authors.initials: S
authors.lastname: Suleman
authors.forename: Bram
authors.initials: B
authors.lastname: Baert
authors.forename: Elien
authors.initials: E
authors.lastname: Vangheluwe
authors.forename: Sylvia
authors.initials: S
authors.lastname: Van Dorpe
authors.forename: Christian
authors.initials: C
authors.lastname: Burvenich
authors.forename: Luc
authors.initials: L
authors.lastname: Duchateau
authors.forename: Frans H
authors.initials: FH
authors.lastname: Jansen
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D003198:Computer Simulation; D004355:Drug Stability; D004983:Ethanolamines / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D000078102:Lumefantrine
chemical_list: D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine