PHENOLIC METABOLITES OF DL-NORGESTREL: A METHOD FOR THE REMOVAL OF 1-HYDROXYLATED METABOLITES, POTENTIAL SOURCES OF PHENOLIC ARTIFACTS

1974 ◽  
Vol 76 (4) ◽  
pp. 789-800 ◽  
Author(s):  
Samuel F. Sisenwine ◽  
Ann L. Liu ◽  
Hazel B. Kimmel ◽  
Hans W. Ruelius
Keyword(s):  
Urinary Metabolites ◽  
Ion Exchange Resin ◽  
Gas Chromatography Mass Spectrometry ◽  
Phenolic Metabolites ◽  
Hydroxylated Metabolites ◽  
Analytical Work ◽  
Potential Sources ◽  
Alkaline Conditions ◽  
Artifact Formation ◽  
Work Up

ABSTRACT The identification of 1β-hydroxynorgestrel among the urinary metabolites of dl-norgestrel and the facile transformation of this compound under mild alkaline conditions to a potentially oestrogenic phenol provide an experimental basis for the conclusion advanced by others that the oestrogens present in the urine of subjects treated with synthetic progestens are artifacts formed during analytical work-up. A method has been devised which eliminates 1-hydroxylated metabolites as potential sources of phenolic artifacts. This method is based on the reduction by NaBH4 of the 1-hydroxy-4-en-3-one grouping in the A ring thereby excluding the possibility of aromatization during later fractionation on a basic ion exchange resin that separates neutral from phenolic metabolites. In the urines of women treated with 14C-dl-nogestrel, only 0.17–0.27% of the dose is found to have phenolic properties when this method is used. Two of the phenolic metabolites, 18-homoethynyloestradiol and 16β-hydroxy-18-homoethynyloestradiol, are present in amounts smaller than 0.01 % of the dose. Without the reduction steps the percentages are noticeably higher, indicating artifact formation under alkaline conditions. Similar results were obtained with urines from African Green Monkeys (Cercopithecus Aethiops) that had been dosed with 14C-dl-norgestrel. Radiolabelled 18-homoethynyloestradiol and 16β-hydroxy-18-homoethynyloestradiol were isolated from monkey urine and their identity confirmed by gas chromatography-mass spectrometry.

Urinary metabolites of thromboxane and prostacyclin in diabetes mellitus

1988 ◽  
Vol 118 (2) ◽  
pp. 301-305 ◽  
Author(s):  
K. Gréen ◽  
O. Vesterqvist ◽  
V. Grill
Keyword(s):  
Diabetes Mellitus ◽  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Insulin Treatment ◽  
Artificial Pancreas ◽  
Urinary Metabolites ◽  
Gas Chromatography Mass Spectrometry ◽  
Diabetic State ◽  
In Vivo Synthesis

Abstract. The in vivo synthesis of thromboxane A2 and prostacyclin was estimated in 23 diabetics through measurements of the major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1α utilizing gas chromatography-mass spectrometry. Mean excretion was similar to that in non-diabetic subjects. The possible influence of hyperglycemia on the excretion of 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1α was evaluated in three ways: by measuring excretion before and during an acute 9-h normalization of hyperglycemia through an artificial pancreas (Biostator) as well as by comparing excretion before and 7–12 days or 40–180 days after the initiation of insulin treatment. Despite significant reducing effects on hyperglycemia or on levels of hemoglobin A1c, no effects on the excretion of the thromboxane and prostacyclin metabolites could be found. Abnormal formation of thromboxane or prostacyclin is not a generalized feature of the diabetic state.

3-hydroxydecanedioic acid and related homologues: urinary metabolites in ketoacidosis.

1980 ◽  
Vol 26 (2) ◽  
pp. 261-265 ◽  
Author(s):  
J Greter ◽  
S Lindstedt ◽  
H Seeman ◽  
G Steen
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Gas Chromatography ◽  
Dicarboxylic Acids ◽  
Urinary Metabolites ◽  
Gas Chromatography Mass Spectrometry ◽  
Beta Oxidation ◽  
Silicic Acid Chromatography ◽  
Minor Compounds ◽  
Hexanedioic Acid

Abstract Urine from patients with ketoacidosis was found to contain a number of aliphatic 3-hydroxy dicarboxylic acids. The acids were purified by silicic acid chromatography and their structures determined by gas chromatography-mass spectrometry of different derivatives. The major compound was 3-hydroxydecanedioic acid. Minor compounds were 3-hydroxyoctanedioic acid, 3-hydroxyoctenedioic acid, 3-hydroxydecenedioic acid, 3-hydroxydodecanedioic acid, 3-hydroxydodecenedioic acid, 3-hydroxytetradecenedioic acid, and 3-hydroxytetradecadienedioic acid. The excretion of 3-hydroxydecanedioic acid correlated positively with the excretion of hexanedioic acid, another metabolite constantly found in ketoacidosis (Pettersen et al., Clin. Chim. Acta 38: 17-24, 1972). We suggest that the 3-hydroxy dicarboxylic acids are formed from fatty acids by a combination of omega-oxidation and incomplete beta-oxidation.

3-hydroxydecanedioic acid and related homologues: urinary metabolites in ketoacidosis.

1980 ◽  
Vol 26 (2) ◽  
pp. 261-265
Author(s):  
J Greter ◽  
S Lindstedt ◽  
H Seeman ◽  
G Steen
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Gas Chromatography ◽  
Dicarboxylic Acids ◽  
Urinary Metabolites ◽  
Gas Chromatography Mass Spectrometry ◽  
Beta Oxidation ◽  
Silicic Acid Chromatography ◽  
Minor Compounds ◽  
Hexanedioic Acid

Abstract Urine from patients with ketoacidosis was found to contain a number of aliphatic 3-hydroxy dicarboxylic acids. The acids were purified by silicic acid chromatography and their structures determined by gas chromatography-mass spectrometry of different derivatives. The major compound was 3-hydroxydecanedioic acid. Minor compounds were 3-hydroxyoctanedioic acid, 3-hydroxyoctenedioic acid, 3-hydroxydecenedioic acid, 3-hydroxydodecanedioic acid, 3-hydroxydodecenedioic acid, 3-hydroxytetradecenedioic acid, and 3-hydroxytetradecadienedioic acid. The excretion of 3-hydroxydecanedioic acid correlated positively with the excretion of hexanedioic acid, another metabolite constantly found in ketoacidosis (Pettersen et al., Clin. Chim. Acta 38: 17-24, 1972). We suggest that the 3-hydroxy dicarboxylic acids are formed from fatty acids by a combination of omega-oxidation and incomplete beta-oxidation.

scholarly journals Structure Elucidation of Urinary Metabolites of Fentanyl and Five Fentanyl Analogs using LC-QTOF-MS, Hepatocyte Incubations and Synthesized Reference Standards

2020 ◽  
Author(s):  
Jakob Wallgren ◽  
Svante Vikingsson ◽  
Tobias Rautio ◽  
Enas Nasr ◽  
Anna Åstrand ◽  
...  
Keyword(s):  
Urinary Metabolites ◽  
Reference Standards ◽  
Urine Samples ◽  
Data Sets ◽  
Hydroxylated Metabolites ◽  
Flight Mass Spectrometry ◽  
Starting Point ◽  
Fentanyl Analogs ◽  
Hydroxylated Metabolite

Abstract Fentanyl analogs constitute a particularly dangerous group of new psychoactive compounds responsible for many deaths around the world. Little is known about their metabolism, and studies utilizing liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis of hepatocyte incubations and/or authentic urine samples do not allow for determination of the exact metabolite structures, especially when it comes to hydroxylated metabolites. In this study, seven motifs (2-, 3-, 4- and β-OH as well as 3,4-diOH, 4-OH-3-OMe and 3-OH-4-OMe) of fentanyl and five fentanyl analogs, acetylfentanyl, acrylfentanyl, cyclopropylfentanyl, isobutyrylfentanyl and 4F-isobutyrylfentanyl were synthesized. The reference standards were analyzed by LC-QTOF-MS, which enabled identification of the major metabolites formed in hepatocyte incubations of the studied fentanyls. By comparison with our previous data sets, major urinary metabolites could tentatively be identified. For all analogs, β-OH, 4-OH and 4-OH-3-OMe were identified after hepatocyte incubation. β-OH was the major hydroxylated metabolite for all studied fentanyls, except for acetylfentanyl where 4-OH was more abundant. However, the ratio 4-OH/β-OH was higher in urine samples than in hepatocyte incubations for all studied fentanyls. Also, 3-OH-4-OMe was not detected in any hepatocyte samples, indicating a clear preference for the 4-OH-3-OMe, which was also found to be more abundant in urine compared to hepatocytes. The patterns appear to be consistent across all studied fentanyls and could serve as a starting point in the development of methods and synthesis of reference standards of novel fentanyl analogs where nothing is known about the metabolism.

Searching for new long‐term urinary metabolites of metenolone and drostanolone using gas chromatography–mass spectrometry with a focus on non‐hydrolysed sulfates

2020 ◽  
Vol 12 (8) ◽  
pp. 1041-1053 ◽  
Author(s):  
Aðalheiður Dóra Albertsdóttir ◽  
Wim Van Gansbeke ◽  
Gilles Coppieters ◽  
Kyzylkul Balgimbekova ◽  
Peter Van Eenoo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Urinary Metabolites ◽  
Gas Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry
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