Determination of mefloquine by electron-capture gas chromatography after phosgene derivatization in biological samples and in capillary blood collected on filter paper.
Mefloquine is determined in 100-microliter samples of whole blood, plasma and capillary blood collected on filter paper by gas chromatography with electron-capture detection after derivatization with phosgene. Sample preparation for whole blood and plasma involves a protein precipitation step that uses a combination of zinc and acetonitrile, followed by simultaneous extraction with methylene chloride and derivatization with phosgene at pH 9.50. Filter paper spots are immersed for 12-24 h in 0.1 M hydrochloric acid, followed by simultaneous extraction with methyl tert.-butyl ether and derivatization. After evaporation of the organic phase and reconstitution with ethyl acetate, 1 microliter of the extract is injected into a megabore capillary column. Because of the high sensitivity of the method, mefloquine concentrations down to 25 nmol/l (9.5 micrograms/l) are determined in 100-microliters samples with a relative standard deviation of 12% at the 25 nmol/l level. Excellent precision was obtained over the range of concentrations tested, 0.10-3 mumol/l (45-1100 micrograms/l), in both plasma and whole blood and from filter-paper-collected capillary blood. The day-to-day relative standard deviation in plasma at the therapeutic level (1-3 mumol/l) was 4.5% (n = 8).
Bergqvist
Y
Y
Department of Clinical Chemistry, Falun Central Hospital, Sweden.
Churchill
F C
FC
Mount
D L
DL
D000962:Antimalarials / Q000097:blood*; D002849:Chromatography, Gas; D003500:Cyclization; D004563:Electrochemistry; D005374:Filtration; D006801:Humans; D015767:Mefloquine; D010209:Paper; D010705:Phosgene; D011804:Quinolines / Q000097:blood*
D000962:Antimalarials; D011804:Quinolines; D010705:Phosgene; D015767:Mefloquine