Thesis (Ph. D.)--Institute of Paper Chemistry, 1961. / Includes bibliographical references (p. 47-49).

The fungus Cunninghamella elegans has in many studies shown to have abiotransformation similar to the metabolism of mammals. If the biotransformation isgeneral, it enables the production of metabolites by the fungus and the use asreference material. The purpose of the project were to examine whether themetabolic process of C. elegans is general, with respect to the formation ofglucosides, and can be applied to different classes of drugs. During the project, theanalyses were performed on a UPLC Q-TOF, run in both MSE and MSMS mode. Themobile phase used consisted of MeOH and 0.1 % formic acid in MQ water. Toincrease the concentration of possible glucosides, the samples were subjected to anacidic or alkaline SPE. Glucosides were detected in the fungal incubates of diclofenac,buprenorphine, norbuprenorphine and oxazepam. For diclofenac, besides twodifferent glucosides (diclofenac glucoside and hydroxylated diclofenac glucoside), ahydroxylated metabolite and a hydroxylated metabolite conjugated with sulfate werediscovered. In the samples containing buprenorphine, the phase I metabolitenorbuprenorphine was also encountered. Further, in the fungal incubates ofdexamethasone a defluorinated metabolite was identified, which is a metabolicpathway never before described for C. elegans.ISSN: 1650

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 43-51). Also available on the World Wide Web.

<p>Mass spectrometry (MS) alone or coupled with high-performance liquid chromatography (HPLC) or gas chromatography (GC) is a versatile analytical tool that is routinely employed for identification of unknown compounds in complex mixtures. MS operates by separating ionized analytes based on their mass-to-charge (<i>m/z</i>) ratios. If the analyte can be ionized without complete fragmentation, MS provides molecular weight information and, if performed at high resolution, elemental compositions for the ionized analytes. Tandem mass spectrometry (MSⁿ, n <u>></u> 2 where each MS step corresponds to an ion isolation or separation event) also provides structural information of ionized analytes. With this approach, structural information of the ionized analytes is obtained by isolating the ionized analytes of interest and subjecting them to fragmentation experiments, such as collision-activated dissociation (CAD). The ions of interest can also be isolated and allowed to react with gaseous molecules to generate product ions (ion-molecule reactions). </p> The experiments described in this dissertation focused on the development of tandem mass spectrometry methods based on CAD and/or gas-phase ion-molecule reactions for the differentiation of acyl, <i>N</i>- and <i>O</i>-glucuronide drug metabolites and for identification of primary carbamates as potentially mutagenic impurities. Further, by using a previously published method titled Distillation, Precipitation, Fractionation Mass Spectrometry (DPF MS), the chemical compositions of five crude oil samples, including heavy, medium, and light crude oils with different API gravities, were determined. Additionally, the gravimetric percentages of different compound classes found in these crude oils are reported as well as the correlations found between API gravities and the chemical compositions of crude oils.

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 3 uppsatser.

The effect of a self-selected and semisynthetic diet on urinary conjugates levels was determined in 18 male adults (22-40 y). Urinary conjugates were also quantified to develop an index of detoxification using a multivariate approach. The four major urinary conjugates measured were glucuronides, sulfoconjugates, mercapturates, and amino acid conjugates. Subjects consumed a self-selected diet for three days and a semisynthetic diet for seven days. Mercapturates and amino acid conjugates were most affected by dietary change, excretion levels reduced by about 50% during the semisynthetic diet period (0.27±0.11 vs 0.14±0.02 mmol/24-h; 5.99 vs 3.03 mmol/24-h, respectively). Glucuronides were the least responsive to dietary change with no significant difference between the means of the two diet periods (self-selected diet 2.93±0.77; semisynthetic 3.21±0.29 mmol/24-h). Four methods for developing 'normal' ranges were presented: mean±SD; percentiles; principal component analysis (princomp); Mahalanobis distance (distquan). The four methods were compared. In summary, conjugate excretion levels were found to be sensitive to dietary changes, with some pathways more responsive than others. Also, the princomp and distquan methods were stressed because they are a multivariate approach which combine values for all three pathways and their interaction into a single value that would then be representative of an individual's total, or overall, detoxification level relative to the others in this group. / Ph. D.

The aim of this diploma thesis was the development of a screening method for analysis of 17 benzodiazepines in urine samples using ultra high-performance liquid chromatography with tandem mass spectrometric detection. The partial task was to optimize the conditions for the enzymatic hydrolysis of benzodiazepine glucuronides present in urine using design of experiments (DOE). The optimized chromatographic system consisted of a Zorbax Eclipse Plus Phenyl-Hexyl RRHD column (100 × 2.1 mm, 1.8 μm) and mobile phase consisting of water with 0.1 % acetic acid (component A) and acetonitrile with 0.1 % acetic acid (component B) in various ratios according to the gradient program. Flow rate was 0.2 ml/min, column temperature was 40 řC, and total analysis time was 12 min. Calibration curves for all analytes were measured under optimized conditions in methanol and urine. After optimal detection conditions for oxazepam-glucuronide were found, oxazepam glucuronide was hydrolysed using β-glucuronidase from the abalone to confirm the functionality of the enzyme within the pilot experiment. Optimization of enzymatic hydrolysis conditions via 27 experiments proposed by program Minitab 16 using the Box-Behnken design will be realized later.