Subject(s)
Fat Emulsions, Intravenous , Food Contamination , Europe , Pharmacopoeias as Topic , United StatesABSTRACT
9,10-epoxyoctadecanoic acid has been detected in human urine. Two simple purification procedures were used; the one based upon liquid-liquid extraction and the other based upon sorbent extraction technology isolating the free fatty acid fraction. Prior to trimethylsilylation and gas chromatographic-mass spectrometric analysis, both the epoxy and carboxy functions were reduced to hydroxy groups. The shift in fragmentation of a deuterated sample verified the presence of intact epoxide prior to chemical reduction. Special attention was paid to the risk of false identification of the epoxide. The content of 9,10-epoxyoctadecanoic acid in human urine was estimated to be 2.1 nM/L.
Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Stearic Acids/urine , Deuterium , Fatty Acids, Nonesterified/urine , Gas Chromatography-Mass Spectrometry/statistics & numerical data , Hexanes , Humans , Oxidation-Reduction , Sensitivity and Specificity , Sodium HydroxideABSTRACT
The mutagenicity of senna glycosides and extracts of senna folium and senna fructus was investigated in the Salmonella typhimurium reversion assay. Senna glycosides were inactive in all strains, except for a slight, but significant increase in mutant frequency in TA102 in the absence and presence of liver microsomes. Extracts of senna fructus and senna folium demonstrated weak activity in TA97a, TA100 and TA102 in the presence of liver microsomes, and in TA97a and TA102 in the absence of liver microsomes. A strong increase in mutant frequency (3- to 5-fold above background frequency) was observed with all extracts in TA98 in the presence of liver microsomes. This activity increased further following enzymatic hydrolysis with hesperidinase of extracts of senna fructus from one source, and could be correlated to the release of the flavonol aglycones kaempferol and quercetin. The weak or lacking activity of anthraquinone aglycones in the tested strains of Salmonella typhimurium indicates that mutagenicity can not be attributed solely to the anthraquinone content of these plant materials. The chemical nature of other mutagenic components has not been elucidated.
Subject(s)
Anthraquinones/toxicity , Flavonoids , Kaempferols , Mutagens/toxicity , Senna Extract/toxicity , Animals , Biotransformation , Chromatography, High Pressure Liquid , Emodin/toxicity , Glycoside Hydrolases/metabolism , Microsomes, Liver/metabolism , Quercetin/analogs & derivatives , Quercetin/toxicity , Rats , Salmonella typhimurium/drug effects , Salmonella typhimurium/geneticsABSTRACT
Semipreparative liquid chromatographic separation and subsequent off-line mass spectrometry have revealed caprolactam as a new contaminant in intravenous solutions. The content of the lactam was found to be 1.2-15.0 mg l-1 determined by liquid chromatography. Contamination is attributed to migration of caprolactam from the protecting plastic envelope through the PVC barrier and into the intravenous solution. Migration occurs during the final heat sterilization process.
Subject(s)
Caprolactam/isolation & purification , Drug Contamination , Chromatography, High Pressure Liquid , Injections, Intravenous , Polyvinyl Chloride , Solutions/chemistryABSTRACT
Four triene monoepoxides of arachidonic acid have been identified as endogenous components of human plasma, the epoxy groups being in the 5,6-, 8,9-, 11,12- and 14,15-positions. Prior to trimethylsilylation and gas chromatographic-mass spectrometric analysis, both the expoxy and ester functions were reduced to hydroxy groups and the double bonds were hydrogenated catalytically. Saturation of the double bonds gave diagnostic spectra that were suitable for elucidating the position of the epoxy group. The shift in the fragmentation of a deuteriated sample verified the presence of the intact epoxides prior to chemical reduction. The presence of the double bonds in the epoxy molecules was demonstrated by reduction using homogeneous catalysis with tris(triphenylphosphine)rhodium(I) chloride and deuterium.
Subject(s)
8,11,14-Eicosatrienoic Acid/blood , Aluminum Compounds , Fatty Acids, Unsaturated/blood , Gas Chromatography-Mass Spectrometry , Lithium Compounds , 8,11,14-Eicosatrienoic Acid/analogs & derivatives , Aluminum , Deuterium , Humans , Lithium , Molecular Structure , Oxidation-ReductionSubject(s)
Chloroform/analysis , Disinfection , Sodium Hypochlorite/analysis , Sterilization , Chemical Phenomena , ChemistryABSTRACT
In gastric aspirate from a case of severe chlorprothixene poisoning, large amounts (approximately 30% of the chlorprothixene) of a previously unrecognized compound were found and identified tentatively as 2-chlorothioxanthen-9-one by combined GLC-low-resolution mass spectrometry and high-resolution mass spectrometry. The identity of the unknown compound was verified after synthesis of 2-chlorothioxan-then-9-one by two procedures. Only negligible amounts of 2-chlorothioxanthen-9-one were formed when chlorprothixene, dissolved in acids, bases, chloroform-isopropanol, methanol, or gastric fluid, was stored in the dark. However, large amounts of the drug were converted to 2-chlorothioxanthen-9-one upon exposure to UV light. Moreover, considerable quantities of unidentified degradation products were formed when chlorprothixene was exposed to lamp light as well as to UV light. Therefore, samples from cases of acute drug poisoning should be protected from light until analysis.
Subject(s)
Chlorprothixene/poisoning , Gastric Mucosa/metabolism , Chromatography, Gas , Humans , Inhalation , Mass Spectrometry , ThioxanthenesABSTRACT
2,4'-Isobutylphenylpropionic acid (ibuprofen) has previously been demonstrated to yield four urinary metabolites, formed by omega 1-, omega 2- and omega 3-hydroxylation and by a further oxidation of the primary alcohol of the omega 1-hydroxylated metabolite to a carboxyl group. By synthesis and gas chromatography--mass spectrometry the suggested structure of the omega 3-hydroxylated metabolite was verified in the present study. Moreover, a new metabolite, 2,4'-carboxyphenylpropionic acid, was demonstrated to be present in substantial amounts in dialysis fluid from a nephrectomized patient. In such patients ingested drugs cannot be excreted in the urine, but are metabolized to end products. Thus, dialysis fluid may be a convenient medium for studies on drug metabolism.