Measurement of methsuximide and N-desmethylmethsuximide using solid-phase extraction and wide-bore capillary gas chromatography.

A method for the determination of the anti-epileptic drug methsuximide (MSM) and its active metabolite N-desmethylmethsuximide (NDM) is presented. 5-Methyl-5-phenylhydantoin is used as the internal standard. A simple solid-phase extraction procedure utilizing disposable reversed-phase C18 columns is described. Samples are analyzed by gas chromatography with flame ionization detection using a wide-bore capillary column with a permanently bonded, non-polar stationary phase. The MSM assay possesses linearity to 6.0 micrograms/mL, sensitivity to 0.5 microgram/mL, recovery ranging from 93 to 110%, and precision reflected by a SD of +/- 0.37 microgram/mL. The NDM assay displays linearity up to 80.0 micrograms/mL, sensitivity to 5.0 micrograms/mL, recovery of 90 to 100%, and precision reflected by a SD +/- 0.90 microgram/dL. Lack interference is documented for 6 commonly prescribed anti-epileptic drugs and 4 drugs with similar retention times on this stationary phase; only guaifenesin was found to potentially interfere with the determination of methsuximide. We conclude that the method reported here is ideally suited for monitoring therapeutic and toxic levels of this anti-epileptic drug.

Measurement of trazodone using solid-phase extraction and wide-bore capillary gas chromatography with nitrogen-selective detection.

A method for the determination of the antidepressant drug trazodone is presented. 8-Hydroxyloxapine is used as the internal standard. A simple solid-phase extraction procedure utilizing disposable reversed-phase C18 columns is described. Samples are analyzed by gas chromatography with nitrogen-selective detection using a wide-bore capillary column with a permanently bonded, nonpolar stationary phase. The assay possesses linearity to 3.0 micrograms/mL, sensitivity to at least 0.25 microgram/mL, recovery averaging 96%, and between-run precision reflected by a CV of 5.6%. We conclude that the method reported here is ideally suited for monitoring therapeutic and toxic levels of trazodone.

Measurement of antidepressants using solid-phase extraction and wide-bore capillary gas chromatography with nitrogen-selective detection.

A comprehensive method is presented for the determination of nine antidepressant drugs and metabolites in serum: (1) amitriptyline, (2) nortriptyline, (3) imipramine, (4) desipramine, (5) maprotiline, (6) doxepin, (7) desmethyldoxepin, (8) protriptyline, and (9) trimipramine. Chlorimipramine is used as the internal standard. A simple solid-phase extraction procedure utilizing disposable reversed-phase C18 columns is described. Samples are analyzed by gas chromatography with nitrogen-selective detection using a wide-bore capillary column with a permanently bonded, non-polar stationary phase. The assay possesses linearity to 800 ng/mL for maprotiline and 500 ng/mL for the other antidepressants, sensitivity to at least 25 ng/mL, recovery ranging from 96 to 107%, and between-run precision reflected by CVs of 4.4 to 8.1%. Lack of interference is documented for over 27 commonly prescribed drugs. We conclude that the method reported here is ideally suited for monitoring therapeutic and toxic levels of antidepressant drugs.

Population genetics of coagulant factor IX: frequencies of two DNA polymorphisms in five ethnic groups.

Two frequently used restriction-enzyme polymorphisms (RFLPs) of coagulant F.IX, TaqI and XmnI, have been examined in five ethnic groups: white Americans, black Americans, East Indians, Chinese, and Malays. There is a distinct "cline" in the frequencies of both polymorphisms, from white Americans to Malays. The rarer type 2 alleles of both polymorphisms, in which middle recognition sites are present--and which in our sample reach their highest frequencies in white Americans--are marginally higher in four groups of Europeans previously reported by others. The frequencies of the rarer alleles are significantly higher in Europeans than in black Americans and East Indians, and these alleles are essentially absent in Chinese and Malays. The frequency of heterozygosity diminishes in the same order, being zero in Malays for both polymorphisms. The polymorphisms are in strong linkage disequilibrium, and in all groups the type 1 allele for TaqI is disproportionately accompanied by the type 1 allele for XmnI. The paucity of type 2 alleles and the low rate of heterozygosity in four non-European groups suggest that the polymorphisms will be of little diagnostic value south of Gibraltar and east of Suez. This prediction is confirmed by the observed haplotype frequencies in the black American and the Oriental groups.

Uniform chromatographic conditions for quantifying urinary catecholamines, metanephrines, vanillylmandelic acid, 5-hydroxyindoleacetic acid, by liquid chromatography, with electrochemical detection.

Uniform liquid-chromatographic conditions were developed such that we could quantify norepinephrine, epinephrine, normetanephrine, metanephrine, vanillylmandelic acid, and 5-hydroxyindoleacetic acid in urine by using a single mobile phase of monochloroacetic acid and citric acid, 0.1 mol/L each. All compounds were separated on a C18 column and detected electrochemically at a potential of +0.800 V. Optimization of these uniform chromatographic conditions significantly shortens the changeover time required from one assay to another, resulting in a substantial savings of time and cost to the laboratory.