A liquid chromatography high-resolution mass spectrometry in vitro assay to assess metabolism at the injection site of subcutaneously administered therapeutic peptides

Esposito, Simone; Leonibus, Maria Lucia De; Ingenito, Raffaele; Bianchi, Elisabetta; Orsatti, Laura; Monteagudo, Edith

doi:10.1016/j.jpba.2018.07.009

Cited by 38 publications

(6 citation statements)

References 44 publications

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“…The use of peptides as therapeutic agents has increased recently, owing to their high potency, selectivity, tolerability, and safety profiles in humans. − For diagnostics, it is also important to monitor secretion of endogenous peptides such as hormones and cytokines. − For such therapeutic and bioanalytical applications, it is essential to have a sensitive, specific, and accurate method for peptide quantification. To date, various standard methods have been developed for peptide quantification, such as chromatographic assays (LC–MS/MS), electrophoretic immunoassays, radioimmunoassays (RIA), and enzyme linked immunosorbent assays (ELISA). − However, complex instrumentation and high cost limit the application of chromatographic or electrophoretic methods in routine analysis. While ELISA is the classical analytical approach due to its high sensitivity and throughput, repeatability is sometimes an issue, and the ELISA workflow is prohibitive for many applications .…”

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confidence: 99%

Electrochemical Sensing of the Peptide Drug Exendin-4 Using a Versatile Nucleic Acid Nanostructure

2022

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Although endogenous peptides and peptide-based therapeutics are both highly relevant to human health, there are few approaches for sensitive biosensing of this class of molecules with minimized workflow. In this work, we have further expanded on the generalizability of our recently developed DNA nanostructure architecture by applying it to electrochemical (EC) peptide quantification. While DNA-small molecule conjugates were used in a prior work to make sensors for small molecule and protein analytes, here DNA-peptide conjugates were incorporated into the nanostructure at the electrode surfaces, and antibody displacement permitted rapid peptide sensing. Interestingly, multivalent DNA-peptide conjugates were found to be detrimental to the assay readout, yet these effects could be minimized by solution-phase bioconjugation. The final biosensor was validated for quantifying exendin-4 (4.2 kDa)a human glucagon-like peptide-1 receptor agonist important in diabetes therapyfor the first time using EC methods with minimal workflow. The sensor was functional in 98% human serum, and the low nanomolar assay range lies between the injected dose concentration and the therapeutic range, boding well for future applications in therapeutic drug monitoring.

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confidence: 99%

Electrochemical Sensing of the Peptide Drug Exendin-4 Using a Versatile Nucleic Acid Nanostructure

2022

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“…Another popular route for small peptide administration is intranasal; in this case the peptide can be degraded also by proteases in the nasal mucosa. The development of in vitro models that mimic the degradation in these sites can help to improve the prediction of peptide catabolism [26,89,90].…”

Section: Metabolism and Catabolism Of Prohibited Spsmentioning

confidence: 99%

Doping control analysis of small peptides: A decade of progress

Judák

Esposito

Coppieters

et al. 2021

Journal of Chromatography B

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“…Through preclinical trials, it has been possible to assess exenatide's pharmacokinetic and pharmacodynamic profiles, allowing the elaboration of suppositions that may be corroborated during clinical trials. It is important to highlight that preclinical trials data combined with in vitro results regarding therapeutic peptides, such as exenatide, or other biotechnology-based API, enable the establishment of in vitro/in vivo correlations that are important to predict pharmacokinetic and pharmacodynamic profiles, enabling the assessment of the quantity of API that is available to exert therapeutic action [24].…”

Section: Preclinical Trials and Biosimilarity Assessment Monitoringmentioning

confidence: 99%

“…Biological matrices containing exenatide are frequently submitted to protein precipitation [24,67,76]. The precipitant agent of choice is ACN due to the ability to precipitate proteins without degrading the sample.…”

Section: Quantification Techniquesmentioning

confidence: 99%

Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices

Pinho

Fortuna

Falcão

et al. 2019

Journal of Pharmaceutical Analysis

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The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.

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A liquid chromatography high-resolution mass spectrometry in vitro assay to assess metabolism at the injection site of subcutaneously administered therapeutic peptides

Cited by 38 publications

References 44 publications

Electrochemical Sensing of the Peptide Drug Exendin-4 Using a Versatile Nucleic Acid Nanostructure

Electrochemical Sensing of the Peptide Drug Exendin-4 Using a Versatile Nucleic Acid Nanostructure

Doping control analysis of small peptides: A decade of progress

Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices

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