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  • 1
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In order to determine the fraction of an intravenous bolus dose of ketamine which is metabolized in vivo to the corresponding N-desmethyl compound, norketamine, a novel stable isotope technique was developed and applied to a study in rats. Co-injection of equimoiar amounts of deuterium-labeled ketamine and unlabeled norketamine to four animals, followed by gas chromatographic/mass spectrometric analysis of both the administered compounds and deuterium-labeled norketamine in plasma yielded pharmacokinetic data from which the fraction of the parent drug subjected to N-demethylation (fm) was calculated from AUC data to be 36.8 ± 2.4%. It is concluded that this stable isotope co-administration technique represents a powerful approach to the determination of fm, in that the pharmacokinetics of the metabolite of interest, given as the preformed compound and generated in vivo, are determined simultaneously. This experimental design thus obviates the influence of time-dependent changes in metabolite clearance which may complicate the interpretation of studies performed using the classical cross-over design.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Alkoxycarbonyl derivatives of the cysteine-, N-acetylcysteine- and glutathione conjugates of acetaminophen have been prepared in aqueous buffer solutions and their chromatographic and mass spectrometric properties examined. Structurally informative fragmentation patterns of the cysteine- and N-acetylcysteine derivatives were obtained when their methyl esters were subjected to analysis by direct insertion chemical ionization (CH4) mass spectrometry, although field desorption and liquid secondary ion mass spectrometric techniques were required in order to obtain satisfactory spectral data for derivatives of the glutathione adduct. Treatment of ethoxycarbonyl derivatives of the three acetaminophen metabolites with N-methyltrifluoroacetamide-based silylating reagents led to the formation of a common volatile product which was ideally suited to analysis by gas chromatography/electron impact mass spectrometry. A mechanism is proposed for the formation of this novel derivative, which appears to possess a benzo-1,3-thioxalane structure, and its mass spectral characteristics are reported. Finally, the utility of alkoxycarbonyl derivatives for the analysis of drug - thioether conjugates in biological fluids is discussed in terms of their advantages for aqueous phase derivatization, purification by high-performance liquid chromatography and characterization by mass spectrometry.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Rapid Communications in Mass Spectrometry 1 (1987), S. iv 
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: Fast-atom bombardment mass spectrometry of a synthetic renin substrate decapeptide (Pro-His-Pro-Phe-His-Leu-Val-Ile-His-D-Lys) indicated the presence of several of side-products, including a component 12 Da higher in mass. Low-energy collisionally activated decomposition analyses were performed using a hybrid tanden, instrument and demonstrated that the heavier side product had two components, in which the structural modification was either at the N- or the C-terminus. Additional analyses of the N-acetyl derivative indicated that for each component the strucutrual modification blcoked a site of N-acetylation. It is suggested that the formation of these side products is attributable to the generation of formaldehyde, during removal of the histidine protecting group (benzyloxymethyl), which reacts with the N-terminus of the peptide to give an imidazolidinone structure or with the D-lysine ε-amine group to yield an imine. While the precise genesis of the side-products remains speculative, it is clear that the combined strategy of derivatization and tandem mass spectrometry has allowed structural conclusions concerning individual components of an isobaric mixture.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Daughter ion spectra are reported for [M + H]+ ions generated by fast atom bombardment mass spectrometry of S-(N-methylcarbamoyl)glutathione (1) and a series of alkoxycarbonyl methyl ester derivatives thereof. Structurally informative, even-electron fragment ions, which serve to define the nature of both the xenobiotic and peptide components of the conjugate, are observed in the collisionally activated dissociation (CAD) spectra of 1 and its ethoxy- and benzyloxycarbonyl methyl esters. Studies with the t-butyloxycarbonyl (tBOC) methyl ester derivative, on the other hand, indicated that the tBOC group exerts a powerful directing influence on the CAD process, and that the major daughter ions in this case are associated with cleavage of the tBOC functionality itself and are of little diagnostic value. Of the derivatives examined, the benzyloxycarbonyl congener, which may be generated readily from 1 in aqueous media, is judged to be the most useful from the standpoints of ease of formation, desirable high-performance liquid chromatographic properties, and informative mass spectral fragmentation characteristics under CAD conditions.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Rapid Communications in Mass Spectrometry 2 (1988), S. 195-195 
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: Liquid chromatography/thermospray mass spectrometry (LC/TSP-MS) has been used to identify and study the rates of formation of S-(N-methylcarbamoyl) cysteine and S-(N-methylcarbamoyl)glutathione as products of the in vitro reaction of cysteine and glutathione, respectively, with two monomethylcarbamate metabolites of the bronchodilator pro-drug bambuterol. The conjugates of interest afforded MH+ species and yielded abundant structurally informative fragment ions which were employed in the development of quantitative, selected-ion monitoring assays. It is concluded that LC/TSP-MS represents a rapid and convenient approach to the direct aqueous-phase analysis of the class of S-(N-alkylcarbamoyl) conjugates of cysteine and glutathione.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 4 (1986), S. 180-187 
    ISSN: 0736-0266
    Keywords: Autoradiography ; Microautoradiography ; Bone ; Technetium ; Bone-scanning agents ; Diphosphonate ; Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Technetium-99m methylene diphosphonate ([99mTc]MDP) is the most widely used bone-scanning agent today. In order to determine the precise bone locus of 99mTc corresponding to the delayed bone scan image, and to test the potential clinical use of this agent in enhancing the information obtained by bone scan, we employed [99mTc]MDP in this microautoradiographic study of normal bone and bone repairative tissue. Four white rabbits underwent operations in which two 1.5-mm drill holes were created in the subtrochanteric regions of both of their femora. An additional four white rabbits underwent sham operations of their femora, in which neither drilling nor periosteal injury occurred. Two rabbits were controls and did not undergo operation. After 7 days, the first two groups of rabbits were injected with [99mTc]MDP and bone scanned 2 h later. After the scans were completed, all three groups of animals were killed and their femora histologically processed for microautoradiography and routine histopathology. In the two groups that were injected with [99mTc]MDP, all bones showed the isotope to be clearly localized along mineralization fronts. The isotope was occasionally found in the substance of the osteoid, but was absent from the cytoplasm and nuclei of osteoblasts and osteocytes. Osteocytic lacunae showed the presence of isotope at their borders, but no identifiable pattern of isotope uptake was noted. Neither osteoclasts nor Howships lacunae showed isotope uptake. The animals that received drill holes showed corresponding areas of uptake by bone scan, whereas those that did not receive drill holes showed no bone scan activity at these sites. The histological findings were qualitatively similar in the bones from both groups of animals, but were quantitatively greater in the bones undergoing repair. The uninjected animals showed no positive chemography on their slides, indicating that the histological fixing and embedding solutions did not introduce artifacts into the technique. Skeletal scintigraphy has been shown to be a valuable clinical tool in the assessment of pathological conditions of bone. Through the use of microautoradiography, a correlation between the information gained by a bone scan and that of a bone biopsy or excised bony lesion can be made. This may aid in the assessment of the biological behavior of tumors or other pathological conditions of bone, as well as the precision of the bone scan in defining or localizing an osseous lesion.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Hoboken, NJ [u.a.] : Wiley-Blackwell
    Journal of Orthopaedic Research 6 (1988), S. 317-323 
    ISSN: 0736-0266
    Keywords: Bone ; Mechanical properties ; Diabetes ; Streptozocin ; Mineralization ; Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The long-term effects of experimentally induced diabetes on bone were studied in eight male Lewis rats, intravenously (i.v.) injected with 65 mg/kg of streptozocin (STZ) and maintained for 12 months. Eight untreated age-matched rats served as controls. In the STZ-treated rats, experimentally induced diabetes was documented by the presence of hyperglycemia at 24 h and at 3 and 12 months. Significantly less weight was gained and less growth occurred in the STZ-treated rats despite careful attention to feeding and hydration. Mineral alterations were detected in the bones of the animals with experimental diabetes. Decreased hydroxyapatite crystal perfection, decreased Ca/P of the ash, and decreased ash content in the tibial metaphyses with increased ash content in the tibial diaphyses, was noted relative to controls. Bone osteocalcin content was increased in the metaphyses of the STZ-treated rats. While absolute measures of stiffness, torsional strength and energy absorption were decreased in the bones of the STZ-treated animals, when torsional strength and stiffness were normalized for differences in both growth and geometry, the normalized stiffness values for the diabetic bones were increased. The results suggest that in experimental diabetes certain aspects of bone mineralization are adversely affected and lead to reduced strength-related properties. However, a compensatory increase in stiffness occurs. The reason for this increase, although not known, may be related to changes in bone crystal structure.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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