By H. J. Bensted, W. Bulloch, L. Dudgeon, A. G. Gardner, E. D. W. Greig, D. Harvey, W. F. Harvey, T. J. Mackie, R. A. O'Brien, H. M. Perry, H. Scutze, P. Bruce White, W. J. Wilson. London, 1929. His Majesty's Stationery Office. Pp. 1–482
by A. Trevor Willis, M.D., B.S. (Melb.), Ph.D. (Leeds), M.C.Path., M.C.P.A., Reader in Microbiology, Monash University, formerly Lecturer in Bacteriology, University of Leeds. xiv + 234 pages, illustrated, second edition. Butterworth Inc., Washington. 1965. $8.50
Simultaneous Measurement of Proguanil and Its Metabolites in Human Plasma and Urine by Reversed-Phase High-Performance Liquid Chromatography, and Its Preliminary Application in Relation to Genetically Determined S-Mephenytoin 4′-Hydroxylation Status
A simple high-performance liquid chromatographic (HPLC) assay method was developed for the measurement of proguanil (PG) and its major metabolites, cycloguanil (CG) and 4-chlorophenylbiguanide (CPB), in human plasma and urine. The assay allowed the simultaneous determination of all analytes in 1 ml of plasma or 0.1 ml of urine. The detection limits of PG, CG, and CPB, defined as the signal-to-noise ratio of 3, were 1 and 5 ng/ml for plasma and urine samples, respectively. Recoveries of the analytes and the internal standard (pyrimethamine) were > 62% from plasma and > 77% from urine. Intra-assay and interassay coefficients of variation for all analytes in plasma and urine were < 10% except for the values of CG and CPB, which ranged from 10% to 15% at one or two concentrations among 4–5 concentrations studied. The clinical applicability of the method was assessed by the preliminary pharmacokinetic study of PG, CG, and CPB in six healthy volunteers with the individually known phenotypes (extensive and poor metabolizers) of S-mephenytoin 4′-hydroxylation, suggesting that individuals with a poor metabolizer phenotype of S-mephenytoin have a much lower capacity to bioactivate PG to CG compared with the extensive metabolizers.