Chiral chromatographic method to determine the enantiomers of halofantrine and its main chiral desbutyl metabolite in erythrocytes.
We describe a direct liquid chromatographic method with spectrofluorimetric detection to quantify the two enantiomers of halofantrine and the two enantiomers of its main chiral N-monodesbutylated metabolite in erythrocyte pellets. The method involves a Chiralpak AD column and a rapid one-step extraction procedure with acetonitrile. The method was validated for the four enantiomers within the range 0-1000 ng/ml. The absence of stereoconversion was studied in samples stored frozen for up to eight months. The optical rotation of the halofantrine and metabolite enantiomers was determined after separation on a semi-preparative Chiralcel OD column with polarimetric detection.
Gorichon
E
E
Hôpital Pitié Salpêtrière, Service Pharmacie-Pharmacocinétique, Paris, France.
Martin
C
C
Bangchang
K N
KN
Karbwang
J
J
Thuillier
A
A
Farinotti
R
R
Gimenez
F
F
D000284:Administration, Oral; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D004912:Erythrocytes / Q000737:chemistry*; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D010616:Phenanthrenes / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D015203:Reproducibility of Results; D013237:Stereoisomerism
D000962:Antimalarials; D010616:Phenanthrenes; C044961:1,3-dichloro-6-trifluoromethyl-9-phenanthryl-3-(n-butyl)aminopropanol; C023768:halofantrine