34S: A New Opportunity for the Efficient Synthesis of Stable Isotope Labeled Compounds

Ren, Sumei; Fier, Patrick S.; Ren, Hong; Hoover, Andrew J.; Hesk, David; Marques, Rosemary; Mergelsberg, Ingrid

doi:10.1002/chem.201801494

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…Generally, SIL compounds are at least three to four mass units heavier than the parent congener, with no greater than 0.2% of the unlabeled compound present, in order to avoid any overlap between the SIL compound and analyte in bioanalytical mass spectrometry assays. [5] Some compounds containing elements with a naturally wider occurring isotopic distribution, (i.e., S, Cl, or Br), can require a SIL standard with a mass enrichment greater than four in order to avoid signal interference. Developing complex SIL sulfonamide compounds that meet such SIL mass requirements typically involve time consuming multi-step syntheses and extensive chemical derivatization (Figure 2A).…”

Section: Late-stage 18 O Labeling Of Primary Sulfonamides Via a Degramentioning

confidence: 99%

Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

Reilly

Bennett²,

Fier³

et al. 2020

Preprint

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A late-stage 18O labeling approach of sulfonamides that employs the corresponding unlabeled molecule as the starting material was developed. Upon deamination of the sulfonamide, a sulfinate intermediate was isotopically enriched using eco-friendly reagents H218O and 15NH3(aq) to afford a M+5 isotopologue of the parent compound. This degradation-reconstruction approach afforded isolated yields of up to 96% for the stable isotope labeled (SIL) sulfonamides, and was compatible with multiple marketed therapeutics, including celecoxib, on a gram scale. The SIL products also exhibited no 18O/16O back exchange under extreme conditions, further validating the utility of this green strategy for drug labeling for both in vitro and in vivo use. This procedure was also adapted to include pharmaceutically relevant methyl sulfones by using 13CH3, affording M+5 isotopic enrichment, thereby illustrating the broad utility of this methodology.

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Section: Late-stage 18 O Labeling Of Primary Sulfonamides Via a Degramentioning

confidence: 99%

Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

Reilly

Bennett²,

Fier³

et al. 2020

Preprint

Self Cite

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“…However, throughput can be lower than traditional LCMS. Like other techniques, an appropriate IS is needed but stable labeled oligonucleotides have not been routinely used due to the perceived difficulty for production [64]. Typically, a surrogate oligonucleotide can be used as an IS by attempting to match chemistry and stereochemistry to obtain the same extraction efficiency as the analyte.…”

Section: Hybridization Hplc-fl and Lcms/hrms Assay Of Oligonucleotides And Comparison With Hybridization Elisamentioning

confidence: 99%

2018 White Paper on Recent Issues in Bioanalysis: ‘A Global Bioanalytical Community Perspective on Last Decade of Incurred Samples Reanalysis (ISR)’ (Part 1 – Small Molecule Regulated Bioanalysis, Small Molecule Biomarkers, Peptides & Oligonucleotide Bioanalysis)

Welink¹,

Yang

et al. 2018

Bioanalysis

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The 2018 12 th Workshop on Recent Issues in Bioanalysis (12th WRIB) took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small-and largemolecule bioanalysis involving LC-MS, hybrid ligand binding assay (LBA)/LC-MS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for LC-MS for small molecules, peptides, oligonucleotides and small molecule biomarkers. Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) and Part 3 (large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays) are published in volume 10 of Bioanalysis, issues 23 and 24 (2018), respectively.

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“…In recent years, liquid chromatography-mass spectrometry (LC–MS) and ultra-high-performance liquid chromatography (UPLC) systems have been developed to facilitate the analysis of many substances at the same time with high sensitivity and selectivity 20 . Stable isotope-labeled compounds have also been employed in several areas of biomedical research 21 . The combination of stable isotope-labeling techniques with MS has allowed rapid acquisition and interpretation of data and has been used in many fields, including distribution, metabolism, food, and excretion studies 22–24 .…”

Section: Introductionmentioning

confidence: 99%

Tracing the mass flow from glucose and phenylalanine to pinoresinol and its glycosides in Phomopsis sp. XP-8 using stable isotope assisted TOF-MS

Zhang

Shi

et al. 2019

Sci Rep

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Phomopsis sp. XP-8, an endophytic fungus from the bark of Tu-Chung (Eucommia ulmoides Oliv) showed capability to biosynthesize pinoresinol (Pin) and pinoresinol diglucoside (PDG) from glucose (glu) and phenylalanine (Phe). To verify the mass flow in the biosynthesis pathway, [13C6]-labeled glu and [13C6]-labeled Phe were separately fed to the strain as sole substrates and [13C6]-labeled products were detected by ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry. As results, [13C6]-labeled Phe was incorporated into [13C6]-cinnamylic acid (Ca) and p-coumaric acid (p-Co), and [13C12]-labeled Pin, which revealed that the Pin benzene ring came from Phe via the phenylpropane pathway. [13C6]-Labeled Ca and p-Co, [13C12]-labeled Pin, [13C18]-labeled pinoresinol monoglucoside (PMG), and [13C18]-labeled PDG products were found when [13C6]-labeled glu was used, demonstrating that the benzene ring and glucoside of PDG originated from glu. It was also determined that PMG was not the direct precursor of PDG in the biosynthetic pathway. The study identified the occurrence of phenylalanine- lignan biosynthesis pathway in fungi at the level of mass flow.

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³⁴S: A New Opportunity for the Efficient Synthesis of Stable Isotope Labeled Compounds

Cited by 7 publications

References 23 publications

Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

2018 White Paper on Recent Issues in Bioanalysis: ‘A Global Bioanalytical Community Perspective on Last Decade of Incurred Samples Reanalysis (ISR)’ (Part 1 – Small Molecule Regulated Bioanalysis, Small Molecule Biomarkers, Peptides & Oligonucleotide Bioanalysis)

Tracing the mass flow from glucose and phenylalanine to pinoresinol and its glycosides in Phomopsis sp. XP-8 using stable isotope assisted TOF-MS

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