Mary L. Holland

Urinary profiles of volatile and acid metabolites in germfree and conventional rats

Qualitative and quantitative differences in the urinary excretion of volatile and acidic metabolites in germfree and conventional rats were examined by capillary gas chromatography and gas chromatography/mass spectrometry. A number of carbonyl compounds, including several short-chain aliphatic ketones and acetophenone, were higher in the conventional urines, while many heterocyclic compounds (furan derivatives, benzothiazole and others) were lower. Both qualitative and quantitative differences were observed in the urinary excretion of acidic metabolites. Three meta-hydroxy phenolic acids appeared only in the conventional rat urines, while levels of many other aromatic and aliphatic acids were also higher.

Structural relationships between the endogenous volatile urinary metabolites of experimentally diabetic rats and certain neurotoxins

High resolution glass capillary gas chromatography and GC/MS were utilized to examine qualitative and quantitative variations from normal of urinary volatile metabolites of long-term alloxan and streptozotocin diabetic rats. Volatile metabolites were structurally compared with known neurotoxins to examine any possible relationship between these metabolites and the development of the diabetic polyneuropathy.

Chromatographic profiling of urinary volatile and organic acid metabolites of normal and diabetic C57BL/Ks mice

Capillary gas chromatography and gas chromatography-mass spectrometry were used to examine the urinary volatile and organic acid metabolites in normal and diabetic C57BL/Ks male mice. Quantitative differences in the excretion of these metabolites were assessed in the animals from 5 to 24 weeks of age. Statistically significant differences were examined with respect to known metabolic abnormalities in the diabetic animals and to the possible toxic effects of elevated levels of certain metabolites. A number of aldehyde metabolites and aromatic acids, as well as most other organic acids, were found at consistently higher levels in diabetic urine. Several ketone metabolites, linalool, and 2-sec.-butylthiazoline were found at consistently low levels throughout the study.

Excretion of urinary volatile metabolites in response to alloxan induced diabetes of short duration in rats.

Alterations in urine volatile metabolites due to the induction of alloxan diabetes in the rat were examined by capillary gas chromatography and gas chromatography--mass spectrometry for the five days immediately following the onset of chronic hyperglycemia. Elevations of a number of metabolites were observed including several short chain ketones, acetophenone, 2-acetylfuran and indole. The value of urine volatile metabolic profiles as characteristic indicators of the diabetic condition is demonstrated through profiles obtained from a diabetic animal which spontaneously reverted to normal.

Urinary profiles of organic acids and volatile metabolites during the starvation process in rats.

Capillary gas chromatographic procedures were used to quantify the volatile and acidic compound profiles in the urinary samples of Sprague-Dawley rats during the starvation and refeeding periods. Numerous metabolites, identified through mass spectrometry, showed significant variations due to these physiological processes. Correlations are attempted with the previously studied biochemical processes in diabetic animals.

High-performance liquid chromatographic assay with ultraviolet detection for the determination of etoperidone and two active metabolites, 5-(1-hydroxyethyl)etoperidone and 1-(3-chlorophenyl)piperazine, in plasma

A selective and sensitive high-performance liquid chromatographic assay with ultraviolet detection for the determination of the antidepressant drug etoperidone and two active metabolites in plasma is described. The drug, metabolites and internal standard are isolated from plasma using a two-step liquid-liquid extraction procedure. The resulting sample is chromatographed on a C18 column (10 cm x 2.1 mm I.D.) with ultraviolet detection at 254 nm. Standard curves are linear for each compound over the concentration range 2-1000 ng/ml. The accuracy and precision of the assay, expressed as the percentage deviation of measured values from the true value and the relative standard deviation (inter-run), are less than or equal to 10% at all concentrations except the minimum quantification limit. Using an automated injector and computerized data acquisition, eighty samples can be routinely processed in one day. The assay has been successfully used for the analysis of plasma samples from pharmacokinetic studies in mice, rats, dogs and humans.

Automated capillary gas chromatographic assay using nitrogen-phosphorus ionization detection for the determination of bepridil in human plasma.

A highly sensitive and specific capillary gas chromatographic method for the determination of the antianginal drug bepridil in plasma is described. The capillary gas chromatograph and nitrogen-selective detector combination provides excellent sensitivity for clinical samples. The lowest concentration of bepridil which can be measured accurately and precisely in a 1-ml plasma sample is 1 ng/ml. Standard curves are linear over the concentration range 1-60 ng/ml. Accuracy and precision of the assay, expressed as relative deviation from the true value and relative standard deviation (inter-run) are less than 15% at all concentrations in the linear range. No interfering peaks are observed. Using an automatic injector and a laboratory computer system, sixty samples can be analyzed routinely in one day. The present assay has been successfully cross-validated with a published high-performance liquid chromatographic assay.