An LC-MS/MS method for the simultaneous quantification of 32 steroids in human plasma

Šimková, M; Kolátorová, Lucie; Drašar, Pavel; Vítků, Jana

doi:10.1016/j.jchromb.2022.123294

Cited by 9 publications

(3 citation statements)

References 39 publications

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“…Epiandrosterone (Figure 21) is a natural steroid metabolite of testosterone and dihydrotestosterone found in human plasma and urine [100–102] . A SciFinder ® structure search revealed no follow‐up academic publications of epiandrosterone being used as an SARS‐CoV‐2 PL pro inhibitor but a cell‐based assay involving human coronavirus OC43 revealed an EC 50 of 3.59 μM [103] .…”

Section: Patent Reviewmentioning

confidence: 99%

“…Epiandrosterone (Figure 21) is a natural steroid metabolite of testosterone and dihydrotestosterone found in human ChemMedChem plasma and urine. [100][101][102] A SciFinder ® structure search revealed no follow-up academic publications of epiandrosterone being used as an SARS-CoV-2 PL pro inhibitor but a cell-based assay involving human coronavirus OC43 revealed an EC 50 of 3.59 μM. [103] In comparison, the EC 50 of the CoV M pro inhibitor nirmatrelvir on SARS-CoV-2-infected Vero E6 cells was reported to be 75 � 8 nM, indicating that epiandrosterone lacks sufficient inhibitory activity for use as an antiviral drug to treat COVID-19.…”

Section: Patent Reviewmentioning

confidence: 99%

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A Patent Review on SARS Coronavirus Papain‐Like Protease (PL^pro) Inhibitors

Chia

Lim

2023

ChemMedChem

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The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is an unprecedented global health emergency causing more than 6.6 million fatalities by 31 December 2022. So far, only three antiviral drugs have been granted emergency use authorisation or approved by the FDA. The SARS‐CoV‐2 papain‐like protease (PLpro) is deemed an attractive drug target as it plays an essential role in viral polyprotein processing and pathogenesis although no inhibitors have yet been approved. This patent review discusses coronavirus PLpro inhibitors reported in patents published between 1 January 2003 to 2 March 2023, giving an overview on the inhibitors that have generated commercial interest, especially amongst drug companies.

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Section: Patent Reviewmentioning

confidence: 99%

Section: Patent Reviewmentioning

confidence: 99%

A Patent Review on SARS Coronavirus Papain‐Like Protease (PL^pro) Inhibitors

Chia

Lim

2023

ChemMedChem

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“…This combination allows for good separation performance and high sensitivity and specificity, which is suitable for qualitative and quantitative analysis ( Tang et al., 2022 ). Compared with gas chromatography and mass spectroscopy (GC-MS), LC-MS does not require complex derivatization of samples and is also suitable for samples with poor thermal stability, poor volatilization, and large molecular weights ( Šimková et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive evaluation of the mechanism of Gastrodia elata Blume in ameliorating cerebral ischemia–reperfusion injury based on integrating fecal metabonomics and 16S rDNA sequencing

Ding

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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Gastrodia elata Blume was used to treat stroke and headaches caused by “Feng” for thousands of years. The present study has shown a significant effect of G. elata Blume in improving cerebral ischemia–reperfusion injury (CIRI). However, the mechanism of G. elata Blume in improving CIRI by regulating the intestinal flora has not been reported until now. This research aimed to comprehensively evaluate the mechanism of G. elata Blume in CIRI based on fecal metabolomics and 16S rDNA sequencing. The rat model with CIRI was created based on the Zea Longa method. Enzyme-linked immunosorbent assay (ELISA) was used to monitor the inflammatory factors in rat serum. Damages of brain tissues were observed using hematoxylin and eosin (H&E) staining. Cerebral infarction was observed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The balance of intestinal flora in cecal contents of rats was evaluated by high-throughput sequencing. Changes of metabolites in the intestinal flora were evaluated by fecal metabolomics through Ultra high performance liquid chromatography-orbitrap exploris-mass spectrometer (UHPLC-OE-MS). The area of brain necrosis, cerebral infarction volume, and the contents of inflammatory factors in CIRI rats can be effectively reduced after oral administration of G. elata Blume. CIRI can cause disturbances in the intestinal flora and its associated metabolites. G. elata Blume can significantly regulate the composition of the intestinal microflora. It reversed CIRI-induced changes in the levels of multiple intestinal bacteria, including Prevotellaceae, Coriobacteriaceae; Prevotella, Gamma proteobacteria unclassified, Barnesiella, Escherichia, Shigella; uncultured Shigella sp., Flavonifractor sp., Escherichia sp. enrichment culture clone NBAR004, Veillonella sp. R-32, and Lactobacillus intestinalis. The levels of metabolites in cecal contents were disturbed in rats with CIRI, including amino acid, purine, and sphingolipid metabolism. The changes in the level of biomarkers in amino acid metabolism induced by CIRI were significantly reversed after treatment with G. elata Blume. Correlation studies show that Prevotellaceae was significantly positively correlated with interleukin (IL)-6, and L. intestinalis and L-phenylalanine were negatively interrelated to IL-1β. Beta-glycerophosphoric acid was significantly negatively interrelated to high-sensitivity C-reactive protein (hs-CRP). There were significantly negative correlations between L-phenylalanine and L. intestinalis, beta-glycerophosphoric acid and Prevotellaceae. G. elata Blume protected against CIRI, which may be related to improved intestinal microflora composition and metabolism, resulting in decreased inflammation.

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Methylation of phase II metabolites of endogenous anabolic androgenic steroids to improve analytical performance

Pfeffer,

Gmeiner,

Forsdahl

2024

Drug Testing and Analysis

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The study of intact phase II metabolites of endogenous anabolic androgenic steroids (EAAS) gives important information about metabolism and has the potential to improve the detection of doping with testosterone. For analysis with liquid chromatography–mass spectrometry (LC‐MS), chemical derivatization at the steroid moiety is a technique to improve the positive ionization efficiency of glucuronidated/sulfated EAAS under collision‐induced dissociation (CID) conditions. However, regarding the chromatographic performance, there are still challenges to address, for example, poor peak shape, which is mainly caused by nondefined adsorption in the chromatographic system. Here, we show a novel derivatization technique for the analysis of selected phase II metabolites of EAAS, where the acidic moiety of the glucuronide/sulfate is methylated with different methylation reagents to reduce nondefined adsorption. The methylation reagent trimethylsilyl‐diazomethane (TMSD) was preferred over the other tested reagents methyl iodide (MeI) and dimethyl sulfate (DMS). Glucuronidated and sulfated testosterone and epitestosterone were methylated, and their chromatographic performance and CID ion mass spectra obtained in positive ionization mode were investigated. The peak width and peak height were significantly improved for all substances. Methylated testosterone sulfate showed the best results with a 3.5 times narrower peak and 14 times increased intensity compared with underivatized testosterone sulfate. Furthermore, CID ion mass spectra obtained in positive ionization mode showed product ions characteristically for the steroidal backbone for all substances. This preliminary study shows the potential of methylation as a supplementary derivatization technique, which can assist in the development of more sensitive methods due to the improvements in method performance.

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An LC-MS/MS method for the simultaneous quantification of 32 steroids in human plasma

Cited by 9 publications

References 39 publications

A Patent Review on SARS Coronavirus Papain‐Like Protease (PL^pro) Inhibitors

A Patent Review on SARS Coronavirus Papain‐Like Protease (PL^pro) Inhibitors

Comprehensive evaluation of the mechanism of Gastrodia elata Blume in ameliorating cerebral ischemia–reperfusion injury based on integrating fecal metabonomics and 16S rDNA sequencing

Methylation of phase II metabolites of endogenous anabolic androgenic steroids to improve analytical performance

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An LC-MS/MS method for the simultaneous quantification of 32 steroids in human plasma

Cited by 9 publications

References 39 publications

A Patent Review on SARS Coronavirus Papain‐Like Protease (PLpro) Inhibitors

A Patent Review on SARS Coronavirus Papain‐Like Protease (PLpro) Inhibitors

Comprehensive evaluation of the mechanism of Gastrodia elata Blume in ameliorating cerebral ischemia–reperfusion injury based on integrating fecal metabonomics and 16S rDNA sequencing

Methylation of phase II metabolites of endogenous anabolic androgenic steroids to improve analytical performance

Contact Info

Product

Resources

About

A Patent Review on SARS Coronavirus Papain‐Like Protease (PL^pro) Inhibitors

A Patent Review on SARS Coronavirus Papain‐Like Protease (PL^pro) Inhibitors