Stability of artesunate in pharmaceutical solvents.
Stability of artesunate (ART) was established in three pharmaceutical solvents. The chromatographic conditions developed for this study were acetonitrile:potassium phosphate buffer 10 mM (40:60, v:v; pH 2.9) at 0.7 mL min(-1) with UV detection at 220 nm using a short X-Terra RP C18 column (50 mm x 3 mm, 3.5 microm). This isocratic condition led to the separation between ART and its main degradation products (i.e. alpha-DHA and beta-DHA) with analysis time of less than 4 min. The retention factors are 1.49, 2.26 and 2.79 min for alpha-DHA, beta-DHA and ART, respectively. This method was proved linear (r(2)=0.9995), accurate (R.S.D.=0.20), precise (R.S.D.=0.74) and robust. The system performance remained unaffected by pH variation from 2.6 to 3.2 and variation of acetonitrile percentage from 38 to 42. Stability of ART was assessed in ethanol, propylene glycol (PG) and polyethylene glycol 400 (PEG 400). Unfortunately none of these solvents prevented ART from degradation longer than 3 months. In ethanol, significant degradation of ART occurred after 3 months at room temperature and this degradation was characterised by numerous degradation products. In PEG 400, significant degradation was observed after only 1 month, however DHA was the unique degradation product, which is also an efficient anti-malarial drug.
Gaudin
Karen
K
Laboratoire de Chimie Analytique UFR Pharmacie, EA 3677, Bases Thérapeutiques des Inflammations et Infections, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. karen.gaudin@u-bordeaux2.fr
Langlois
Marie-Hélène
MH
Barbaud
Anne
A
Boyer
Chantal
C
Millet
Pascal
P
Fawaz
Fawaz
F
Dubost
Jean-Pierre
JP
D000465:Algorithms; D000962:Antimalarials / Q000032:analysis*; D037621:Artemisinins / Q000032:analysis*; D000077332:Artesunate; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D000431:Ethanol; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000032:analysis*; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D012997:Solvents; D000431:Ethanol; D011092:Polyethylene Glycols; D000077332:Artesunate; D019946:Propylene Glycol