LC-(TIC/EIC)-MS as tool in the analysis of diastereomeric 3,12-aza-analogues of deoxycholic acid

Verzele, Dieter; Goeman, Jan; Madder, Annemieke

doi:10.3998/ark.5550190.0008.a21

Cited by 8 publications

(1 citation statement)

References 2 publications

(6 reference statements)

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“…The evaluated data on LC-MS encompassed TIC data (total ion intensity vs. R.T.), EIC (extracted ion chromatograms), and ECC (extracted compound chromatograms). Only the EIC can be considered a targeted approach (Verzele et al, 2007), while both total ion intensity and molecular feature extraction (ECC data) are seen overall as untargeted analyses (Erny et al, 2016;Martínez-Bueno et al, 2019;Erny and Santos, 2021;Xue et al, 2022). Figure 6 shows an example of ECC of an unknown molecule in metformin samples with average mass = 326.0007 Da and R.T. at 7.3 min.…”

Section: Lc-ms Q-tof Spectrometrymentioning

confidence: 99%

Investigating metformin-active substances from different manufacturing sources by NIR, NMR, high-resolution LC-MS, and chemometric analysis for the prospective classification of legal medicines

Raimondo

Aureli²,

D’Ettorre³

et al. 2023

Front. Anal. Sci.

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Introduction: The characterisation of active substances is an essential tool to ensure the traceability and authenticity of legal medicines. Metformin is a well-established biguanide derivative recommended in oral formulations as a first-line treatment for type 2 diabetes. With its increasing demand, metformin is likely to be an attractive target for falsification and substandard production, thus posing health risks to consumers. Methods that are able to identify even small differences in active pharmaceutical ingredients (APIs) are deemed necessary. The detection of fraudulent practices in APIs is not straightforward, and a single technique that can provide sufficient information to unambiguously address this issue is still not available.Methods: This study investigated an integrated analytical platform based on NIR, 1H-NMR, 13C-NMR, and high-resolution LC-MS combined with chemometrics to profile 32 metformin hydrochloride samples originating from several global authorised manufacturers. The study's aim was to explore differences in the chemical characteristics of metformin hydrochloride APIs to identify or predict a possible classification for each manufacturer in view of prospective authenticity studies. Different pre-processing methods were applied; bucket tables for 1H- and 13C-NMR were obtained, while mass spectrometry data were processed in targeted and untargeted modes. Datasets were individually analysed and merged by a multivariate unsupervised method and performing principal component analysis (PCA). Results and Discussion: The results evidenced differences in cluster behaviour, depending on manufacturers. Each technique has shown a specific clustering tendency, highlighting how different analytical approaches are able to characterise metformin APIs. Some manufacturers’ samples, however, showed similar behaviour independently of the techniques. NIR and 1H-NMR were confirmed as the more predictive techniques if taken individually; 1H-NMR, in particular, achieved good separation between the samples of the two most representative manufacturers. For LC-MS, the targeted approach resulted in a separation in groups clearer than that of the untargeted approach. Nevertheless, the untargeted LC-MS approaches presented in this paper could be a possible alternative to obtaining different information for drug substances, with several different and complex synthetic pathways leading to several unknown impurities. Further grouping of manufacturers emerged by data fusion, highlighting its potential in the traceability of metformin.

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Section: Lc-ms Q-tof Spectrometrymentioning

confidence: 99%

Investigating metformin-active substances from different manufacturing sources by NIR, NMR, high-resolution LC-MS, and chemometric analysis for the prospective classification of legal medicines

Raimondo

Aureli²,

D’Ettorre³

et al. 2023

Front. Anal. Sci.

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Untapped Opportunities of Resin‐to‐Resin Transfer Reactions (RRTR) for the Convergent Assembly of Multivalent Peptide Conjugates

Verzele

García

Madder

2020

Chemistry A European J

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Handling of the individual fragments remains a bottleneck in the convergent assembly of peptides. Overlooked since the emergence of ligation chemistries during the past two decades, so‐called resin‐to‐resin transfer reactions (RRTR) are here described as a strategic shortcut in this context. Condensation of the involved moieties at an acceptor resin is facilitated by shuttling peptide segments directly from a donor resin in a one‐pot fashion. The straightforward synthesis of a sterically constrained 13‐mer peptidosteroid model illustrates the utility of this approach, presenting the first successful application of the RRTR methodology in the field of multivalent design and bioconjugation. Relying on established procedures to generate, monitor and isolate intermediates and products, the solid‐phase nature of the entire strategy allows for the fast construction of polypeptide adducts and libraries thereof. As such, a rejuvenated use and new opportunities for RRTR are reported.

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Synthetic Progress in cMyc‐Max Oncoprotein Miniaturization: Semi‐Online Monitoring Gives Solid‐Phase Access to Hydrophobic b(‐HLH‐)ZIP Peptidosteroid Tweezers

Verzele¹,

Madder²

2012

Eur J Org Chem

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Miniature versions of basic leucine zipper (bZIP) and basic helix–loop–helix zipper (b‐HLH‐ZIP) transcription factors are promising tools for molecular dissection of the genetic information in a post‐genomic context. Despite the opportunities of genome interfering agents based on certain oncogenic zipper proteins, structural mimicry of transcription factors is a delicate undertaking, and experimental fine‐tuning through bottom‐up organic chemistry could benefit from solid‐phase/library approaches. Involved in a variety of human pathologies, we became interested in the miniaturization of the cMyc‐Max b‐HLH‐ZIP oncoprotein, and herein elaborate on our synthetic progress in that direction. A bile acid scaffold was successfully employed as artificial dimerization interface in this new type of transcription factor model. Orthogonality of the applied Alloc/Boc/Fmoc chemistries allowed the synthesis of both homo‐ and heterodimeric peptidosteroid conjugates, covalently restricted with defined geometrical properties. Recognition peptides were assembled through standard Fmoc/tBu solid‐phase peptide synthesis (SPPS) chemistry, assisted by automated procedures for consecutive chain elongation on solid support. Invaluable to monitor present strategy, a photocleavable linker allowed rapid, yet detailed analysis of side chain protected peptide intermediates, liberated from the sampled resin, by reverse‐phase HPLC and MALDI‐TOF‐MS. By decorating each scaffold position with two basic region peptides in a 2 × 2 design, a first generation of unprecedented b(‐HLH‐)ZIP peptidosteroids was efficiently obtained. As such, a versatile methodology amenable to library generation is presented.

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LC-(TIC/EIC)-MS as tool in the analysis of diastereomeric 3,12-aza-analogues of deoxycholic acid

Cited by 8 publications

References 2 publications

Investigating metformin-active substances from different manufacturing sources by NIR, NMR, high-resolution LC-MS, and chemometric analysis for the prospective classification of legal medicines

Investigating metformin-active substances from different manufacturing sources by NIR, NMR, high-resolution LC-MS, and chemometric analysis for the prospective classification of legal medicines

Untapped Opportunities of Resin‐to‐Resin Transfer Reactions (RRTR) for the Convergent Assembly of Multivalent Peptide Conjugates

Synthetic Progress in cMyc‐Max Oncoprotein Miniaturization: Semi‐Online Monitoring Gives Solid‐Phase Access to Hydrophobic b(‐HLH‐)ZIP Peptidosteroid Tweezers

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