Determination of proguanil and metabolites in small sample volumes of whole blood stored on filter paper by high-performance liquid chromatography.
A method is reported for the determination of proguanil and its two metabolites cycloguanil and 4-chlorophenylbiguanide in whole blood and plasma samples obtained by thumbprick and stored dry on filter paper. The sample preparation involves liquid extraction from the filter paper and subsequent solid-phase extraction using C8 Bond-Elut cartridges. Separation and quantification is by a previously reported ion-pairing high-performance liquid chromatographic system with ODS Hypersil as stationary phase and an 50:50 acetonitrile-pH 2 phosphate buffer mobile phase containing 200 mM sodium dodecylsulphate as ion-pairing agent. The analytical characteristics of the method are reported. Representative concentrations are shown as a function of time from a human subject after ingestion of a single 200-mg dose of proguanil hydrochloride. Typical ranges of concentration detected by the proposed method in human subjects were proguanil 12-900 ng/ml, cycloguanil 16-44 ng/ml and 4-chlorophenylbiguanide 1.5-10 ng/ml in whole blood.
Kolawole
J A
JA
University of Jos, Nigeria.
Taylor
R B
RB
Moody
R R
RR
D000962:Antimalarials / Q000097:blood*; D001645:Biguanides / Q000097:blood*; D001800:Blood Specimen Collection; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D002727:Proguanil / Q000097:blood*; D014227:Triazines / Q000097:blood*
D000962:Antimalarials; D001645:Biguanides; D014227:Triazines; C026009:cycloguanil; C025963:4-chlorophenylbiguanide; D002727:Proguanil