Determination of pyrimethamine in human plasma after administration of fansidar of fansidar-mefloquine by means of high-performance liquid chromatography with fluorescence detection.
A sensitive, rapid and selective high-performance liquid chromatographic (HPLC) method has been developed to measure plasma levels of pyrimethamine in human subjects dosed with the antimalarials Fansidar or Fansidar and mefloquine. The drug was extracted from plasma at basic pH with n-butyl chloride-dichloromethane (96:4, v/v) and quantified on a normal-phase HPLC column with fluorescence detection (excitation 290 nm, emission 345 nm). Pyrimethamine was almost quantitatively extracted from plasma in the concentration range 20-200 ng/ml. The sensitivity limit was about 10 ng/ml of plasma, using a 0.5-ml specimen. The method was shown to be specific with respect to the other two components in the antimalarial combinations, namely sulfadoxine and mefloquine, and their metabolites. The assay was applied to pharmacokinetic studies of pyrimethamine in man following the oral administration of Fansidar of Fansidar and mefloquine.
D000962:Antimalarials / Q000097:blood / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005453:Fluorescence; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D015767:Mefloquine; D011739:Pyrimethamine / Q000097:blood* / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*; D013424:Sulfanilamides / Q000494:pharmacology*
D000962:Antimalarials; D004338:Drug Combinations; D011804:Quinolines; D013424:Sulfanilamides; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D015767:Mefloquine; D011739:Pyrimethamine