title: Liquid chromatographic separation and measurement of optical isomers of aminoglutethimide and its acetyl metabolite in plasma, saliva, and urine.
abstract: An accurate and specific liquid chromatographic method for the separation and analysis of the R(+) and S(-) enantiomers of both aminoglutethimide (AG) and its acetylated metabolite (AcAG) in plasma, saliva, and urine is described. The separation was achieved by use of two serial Chiralcel OD columns [cellulose tris(3,5-dimethylphenyl carbamate)] with a mixture of hexane/isopropanol/methanol (65:17.5:17.5, per volume) as a mobile phase. The flow rate was 0.7 ml/min, and the compounds were detected in the effluent spectrophotometrically at 245 nm. The plasma, saliva, or urine sample (300 microliters) was extracted with dichloromethane after the addition of an equal volume of acetate buffer (pH 5.6) to the sample. The extraction recovery of the R(+) and S(-) enantiomers of AG and AcAG from plasma, saliva, and urine at different concentrations under these conditions was > 80.9%. No interference from any endogenous substance or concomitantly used drug was observed. The ratio of the peak area of R(+) and S(-) enantiomers of both AG and AcAG/internal standard was linearly (r > or = 0.995) related to concentration in the range 0.83-40.0 micrograms/ml, and the coefficient of variation (CV) at different concentrations was consistently < or = 13%. We are presently employing this method to study the pharmacokinetics of each of these enantiomers in breast cancer patients.
authors.affiliation: Department of Biological and Medical Research, King Faisal Specialist Hospital.
authors.forename: I A
authors.initials: IA
authors.lastname: Alshowaier
authors.forename: A
authors.initials: A
authors.lastname: el-Yazigi
authors.forename: A
authors.initials: A
authors.lastname: Ezzat
authors.forename: A A
authors.initials: AA
authors.lastname: el-Warith
authors.forename: P J
authors.initials: PJ
authors.lastname: Nicholls
mesh_terms: D000433:1-Propanol / Q000737:chemistry; D000107:Acetylation; D000616:Aminoglutethimide / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine; D018931:Antineoplastic Agents, Hormonal / Q000032:analysis* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine; D001943:Breast Neoplasms / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000432:Methanol / Q000737:chemistry; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D012015:Reference Standards; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006586:Hexanes; D011960:Receptors, Estrogen; D000616:Aminoglutethimide; C026385:n-hexane; C036163:N-acetylaminoglutethimide; D000433:1-Propanol; D000432:Methanol