Equine Metabolites of Norethandrolone: Synthesis of a Series of 19-Nor-17α-pregnanediols and 19-Nor-17α-pregnanetriols

2003 ◽  
Vol 56 (8) ◽  
pp. 829 ◽  
Author(s):  
Andrew R. McKinney ◽  
Damon D. Ridley ◽  
Peter Turner
Keyword(s):  
Anabolic Steroid ◽  
Metabolic Pathways ◽  
Urinary Metabolites ◽  
Urine Samples ◽  
Ethynyl Group ◽  
Stereoselective Reduction ◽  
Critical Step ◽  
Subsequent Modification

A range of 19-nor-17α-pregnanediols and 19-nor-17α-pregnanetriols have been synthesized and used to confirm the structures of major equine urinary metabolites of the synthetic anabolic steroid norethandrolone (1). 19-Nor-5α,17α-pregnane-3α,17β-diol (2), 19-nor-5α,17α-pregnane-3β,17β-diol (4), 19-nor-5β,17α-pregnane-3α,17β-diol (6), and 19-nor-5β,17α-pregnane-3β,17β-diol (7) were prepared by stereoselective reduction of the 3-ene-4-one of norethandrolone. The 19-nor-5α,17α-pregnane-3β,16α,17β-triol (8) and 19-nor-5α,17α-pregnane-3β,16β,17β-triol (9) were prepared from 19-nortestosterone (11) by multistep processes in which the critical step involved Grignard additions to 16-acetoxy-17-ones. The triols (20R)-19-nor-5α,17α-pregnane-3β,17β,20-triol (22) and (20S)-19-nor-5α,17α-pregnane-3β,17β,20-triol (23) were prepared from norethindrone (24) by initial selective A-ring reduction, then subsequent modification of the 17-ethynyl group. By comparison of these compounds with post-administration equine urine samples it was possible to establish A-ring reduction with 3β,5α stereochemistry as well as non-stereospecific 16-hydroxylation and 20-hydroxylation as significant metabolic pathways affecting norethandrolone in the horse.

scholarly journals Urinary metabolites and metabolic pathways of three analogues of 1-phenyl-2-(pyrrolidine-1-yl)pentan-1-one (α-PVP) in humans

2017 ◽  
Vol 22 (2) ◽  
pp. 77-90 ◽  
Author(s):  
Hidenao Kakehashi ◽  
Noriaki Shima ◽  
Hiroe Kamata ◽  
Syuntaro Matsuta ◽  
Shihoko Nakano ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Urinary Metabolites

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.

Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: An observational cohort study

Cephalalgia ◽  
2017 ◽  
Vol 38 (4) ◽  
pp. 707-717 ◽  
Author(s):  
Vincent T Martin ◽  
Janelle R Allen ◽  
Timothy T Houle ◽  
Scott W Powers ◽  
Marielle A Kabbouche ◽  
...  
Keyword(s):  
Pubertal Development ◽  
Urinary Metabolites ◽  
Ovarian Hormones ◽  
Urine Samples ◽  
Standard Deviation Increase ◽  
Separate Model ◽  
Headache Severity ◽  
Headache Onset ◽  
Daily Urine ◽  
Observational Cohort

Background Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty. Aims To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine. Methods This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8–11), pubertal (12–15), and post-pubertal (16–17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates. Results Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR −0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models ( p < 0.017). Conclusion Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.

METABOLISM OF [4-14C]NORETHISTERONE IN WOMEN

1968 ◽  
Vol 41 (2) ◽  
pp. 263-272 ◽  
Author(s):  
SORAYA KAMYAB ◽  
K. FOTHERBY ◽  
A. I. KLOPPER
Keyword(s):  
Phenolic Compounds ◽  
Enzymatic Hydrolysis ◽  
Paper Chromatography ◽  
Human Subjects ◽  
Extraction Procedure ◽  
Urinary Metabolites ◽  
Ethynyl Group ◽  
Simple Reduction

SUMMARY After the administration of norethisterone to seven human subjects 37·4% to 80·6% of the dose was excreted in the urine within 5 days. About half of the urinary radioactivity was extractable after acid or enzymatic hydrolysis and about 80% was extracted by using a serial hydrolytic and extraction procedure. About 15% of the urinary radioactivity was present as sulphate conjugates. About 5% of the urinary radioactivity was present in acidic or phenolic compounds. No metabolism of the ethynyl group seemed to occur and the Girard reaction showed that about half of the urinary metabolites were ketonic. The metabolites in the glucuronide fraction of urine were predominantly more polar on paper chromatography than tetrahydronorethisterone, whereas in the sulphate fraction most of the metabolites had a polarity similar to the simple reduction products of norethisterone. Two days after injection the plasma still contained about 5% of the administered dose.

scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Author(s):  
Dagmara Winiarczyk ◽  
Katarzyna Michalak ◽  
Łukasz Adaszek ◽  
Mateusz Winiarczyk ◽  
Stanisław Winiarczyk
Keyword(s):  
Metabolic Pathways ◽  
Protein Identification ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Urine Samples ◽  
Control Group ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs ◽  
Potential Biomarkers

Abstract This study aimed to identify proteins in the urine of dogs with renal dysfunction during the natural course of babesiosis (n=10) and to compare them with proteins in a control group (n=10) to reveal any potential biomarkers of renal damage. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common to both groups. Characteristic analysis of the 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. Furthermore, it was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins and TGF-β (transforming growth factor β) pathways. These pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and FER tyrosine kinase, which are potential biomarkers of damage during babesiosis in dogs that might indicate early renal injury.

scholarly journals Influence of Storage Conditions and Preservatives on Metabolite Fingerprints in Urine

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 203 ◽  
Author(s):  
Xinchen Wang ◽  
Haiwei Gu ◽  
Susana A. Palma-Duran ◽  
Andres Fierro ◽  
Paniz Jasbi ◽  
...  
Keyword(s):  
Large Scale ◽  
Storage Time ◽  
Storage Temperature ◽  
Urinary Metabolites ◽  
Storage Conditions ◽  
Inhibitory Effect ◽  
Urine Samples ◽  
C Storage ◽  
Liquid Chromatography Tandem Mass ◽  
The Stability

Human urine, which is rich in metabolites, provides valuable approaches for biomarker measurement. Maintaining the stability of metabolites in urine is critical for accurate and reliable research results and subsequent interpretation. In this study, the effect of storage temperature (4, 22, and 40 °C), storage time (24 and 48 h), and use of preservatives (boric acid (BA), thymol) and para-aminobenzoic acid (PABA) on urinary metabolites in the pooled urine samples from 20 participants was systematically investigated using large-scale targeted liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics. Statistical analysis of 158 reliably detected metabolites showed that metabolites in urine with no preservative remained stable at 4 °C for 24 and 48 h as well as at 22 °C for 24 h, but significant metabolite differences were observed in urine stored at 22 °C for 48 h and at 40 °C. The mere addition of BA caused metabolite changes. Thymol was observed to be effective in maintaining metabolite stability in urine in all the conditions designed, most likely due to the inhibitory effect of thymol on urine microbiota. Our results provide valuable urine preservation guidance during sample storage, which is essential for obtaining reliable, accurate, and reproducible analytical results from urine samples.

scholarly journals Urine Metabolome during Parturition

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 290
Author(s):  
Federica Gevi ◽  
Alessandra Meloni ◽  
Rossella Mereu ◽  
Veronica Lelli ◽  
Antonella Chiodo ◽  
...  
Keyword(s):  
Urinary Metabolites ◽  
Ultra Performance Liquid Chromatography ◽  
Complete Separation ◽  
Urine Samples ◽  
Hydrophilic Interaction ◽  
Multivariate Statistical ◽  
Highly Sensitive ◽  
Powerful Approach ◽  
The Difference ◽  
Invasive Techniques

In recent years, some studies have described metabolic changes during human childbirth labor. Metabolomics today is recognized as a powerful approach in a prenatal research context, since it can provide detailed information during pregnancy and it may enable the identification of biomarkers with potential diagnostic or predictive. This is an observational, longitudinal, prospective cohort study of a total of 51 serial urine samples from 15 healthy pregnant women, aged 29–40 years, which were collected before the onset of labor (out of labor, OL). In the same women, during labor (in labor or dilating phase, IL-DP). Samples were analyzed by hydrophilic interaction ultra-performance liquid chromatography coupled with mass spectrometry (HILIC-UPLC-MS), a highly sensitive, accurate, and unbiased approach. Metabolites were then subjected to multivariate statistical analysis and grouped by metabolic pathway. This method was used to identify the potential biomarkers. The top 20 most discriminative metabolites contributing to the complete separation of OL and IL-DP were identified. Urinary metabolites displaying the largest differences between OL and IL-DP belonged to steroid hormone, particularly conjugated estrogens and amino acids much of this difference is determined by the fetal contribution. In addition, our results highlighted the efficacy of using urine samples instead of more invasive techniques to evaluate the difference in metabolic analysis between OL and IL-DP.

Free and conjugated catecholamines and metabolites in cat urine after hypoxia

1982 ◽  
Vol 52 (2) ◽  
pp. 304-308 ◽  
Author(s):  
J. Claustre ◽  
L. Peyrin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Renal Function ◽  
Sodium Excretion ◽  
Urinary Metabolites ◽  
Urine Samples ◽  
Hypoxic Stress ◽  
The Central Nervous System ◽  
Sympathetic Nervous ◽  
Da Release

Catecholamine and metabolite excretion was studied in the cat after 6 h of 7.5% O2 hypoxia. Norepinephrine (NE) release from sympathetic nervous endings was strongly activated, whereas epinephrine (E) excretion was only slightly increased. A noteworthy result was the increase of dopamine (DA) and its metabolites [3-methoxytyramine (MT); 3,4-dihydroxyphenylacetic acid (DOPAC)] in urine samples. This increased release does not seem to originate from the central nervous system, but rather from peripheral dopaminergic structures; available knowledge on peripheral DA suggests that the hypoxia-induced DA release might be partly related to chemosensory or renal function. Indeed, in addition to enhanced DA and NE excretion, we observed an increase in sodium excretion that correlated with both DA and NE. Analysis of free and conjugated urinary metabolites showed that only free NE and both free and conjugated normetanephrine were increased in urine after hypoxic stress. Among DA metabolites, conjugated DOPAC was the main DA metabolite in the basal state and after hypoxia. Both the free and the conjugated forms of DA, MT, and DOPAC were increased by hypoxia.

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