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E H Kerns

Publications and source records attributed to E H Kerns.

22 records · Page 2Linked to original sources
PubMed1985

Gas chromatographic-mass spectrometric method for trazodone and a deuterated analogue in plasma.

A plasma assay method for trazodone and a 2H4 analogue is described which uses gas chromatography--electron-impact selected-ion monitoring mass spectrometry. Etoperidone is used as an internal standard. The analytes are extracted from basic medium into n-butyl chloride, then back extracted into aqueous 0.1 M hydrochloric acid. The aqueous layer is made basic and re-extracted with n-butyl chloride. The solvent is reduced under nitrogen at 35 degrees C and the residue is redissolved in toluene for gas chromatographic--mass spectrometric analysis. The ions monitored are m/z 231, 235, and 225 for trazodone, [2H4] trazodone and etoperidone, respectively. Quantitation is in the range 40-1000 ng/ml with acceptable precision and accuracy. The method is suitable for biopharmaceutical studies.

Biological Availability↗
PubMedDate not supplied

LC/MS applications in drug development.

The combination of high-performance liquid chromatography and mass spectrometry (LC/MS) has had a significant impact on drug development over the past decade. Continual improvements in LC/MS interface technologies combined with powerful features for structure analysis, qualitative and quantitative, have resulted in a widened scope of application. These improvements coincided with breakthroughs in combinatorial chemistry, molecular biology, and an overall industry trend of accelerated development. New technologies have created a situation where the rate of sample generation far exceeds the rate of sample analysis. As a result, new paradigms for the analysis of drugs and related substances have been developed. The growth in LC/MS applications has been extensive, with retention time and molecular weight emerging as essential analytical features from drug target to product. LC/MS-based methodologies that involve automation, predictive or surrogate models, and open access systems have become a permanent fixture in the drug development landscape. An iterative cycle of "what is it?" and "how much is there?" continues to fuel the tremendous growth of LC/MS in the pharmaceutical industry. During this time, LC/MS has become widely accepted as an integral part of the drug development process. This review describes the utility of LC/MS techniques for accelerated drug development and provides a perspective on the significant changes in strategies for pharmaceutical analysis. Future applications of LC/MS technologies for accelerated drug development and emerging industry trends are also discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma.

Metabolism of the antidepressant drug nefazodone was studied in humans after single and multiple 50 and 200 mg oral doses of [14C] nefazodone as part of a single and multiple dose balance study. Deuterium was included in the molecule to facilitate structural characterization of the metabolites by mass spectrometry. Metabolites were isolated from a 0-24 hr pooled urine from three subjects and purified to homogeneity by HPLC. Chemical structures of the metabolites were proposed based on collisionally induced dissociation (CID) and electron impact ionization MS. The profile of radioactivity showed three main urinary metabolites, one of which was a conjugate, and several minor metabolites. The three major metabolites were identified as the phenoxyethyl triazolone propionic acid resulting from N-dealkylation of both nefazodone and hydroxynefazodone (OH-Nef), as well as a corresponding phenoxyethyl triazolone propanol metabolite of N-dealkylated nefazodone, present exclusively as a conjugate. The more polar minor components were not identified. The excretion of total radioactivity in the 24-hr sample was 49% of the dose, of which the identified metabolites comprised 38% of the dose. There was no difference in the qualitative or quantitative urinary profile of the metabolites at 50 or 200 mg dose levels after single or multiple oral dosing. These N-dealkylated metabolites were also present in pooled human plasma samples along with nefazodone, OH-Nef, and an unknown metabolite that was present in plasma in large amounts relative to nefazodone and OH-Nef. This metabolite was isolated from plasma and from a human liver S9 incubation and identified by CID tandem MS and NMR as the triazoledione of nefazodone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗