Bridging approaches to facilitate innovation: building an approach for heated tobacco products from case studies in the food and drug domains a comparative review

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Май 21, 2025

Abstract An increasing number of heated tobacco products (HTPs) have been commercialized in several countries over the last decade. To benefit public health, these should a lower health risk profile than cigarettes. This includes need to be sufficiently acceptable adults who smoke so that reasonable proportion those do not want quit smoking are persuaded switch completely. Additionally, product increase likelihood non-smokers starting use or smokers their total consumption products. Part this process involves iterative development new versions, leveraging lessons learned from consumer experiences with marketed products, and applying novel technologies improve offering. Risk assessment for may include pre-clinical quality, analytical toxicity evaluations, pre-market clinical studies, post-market surveillance studies. In recent years, approaches bridge modified data generated reference by comparing equivalence were proposed. Here, we review taken such bridging studies relate them comparability established diverse range pharmaceutical leads proposal logical, stepwise, tiered approach effectively manage introduction HTPs through scientific substantiation potential reducing improving acceptability adult without attracting innovations.

Язык: Английский

---

Protein-Centric Analysis of Personalized Antibody Repertoires Using LC-MS-Based Fab-Profiling on a timsTOF

Journal of the American Society for Mass Spectrometry, Год журнала: 2024, Номер 35(6), С. 1292 - 1300

Опубликована: Апрель 25, 2024

Endogenous antibodies, or immunoglobulins (Igs), abundantly present in body fluids, represent some of the most challenging samples to analyze, largely due immense variability their sequences and concentrations. It has been estimated that our can produce billions different Ig proteins with isotypes, making individual analysis seemingly impossible. However, recent advances protein-centric proteomics using LC-MS coupled Orbitrap mass analyzers profile intact Fab fragments formed by selective cleavage at IgG-hinge revealed IgG repertoires may be less diverse, albeit unique for each donor. Serum seem dominated a few hundred clones cumulatively make up 50–95% total content. Enabling such analyses required careful optimization chromatography analysis, as all analytes are highly alike (46–51 kDa) sequence. To extend opportunities this mass-spectrometry-based profiling antibody repertoires, we here report evaluation an alternative MS platform, namely, timsTOF, repertoire profiling. The timsTOF analyzer gained traction years peptide-centric found wide applicability plasma proteomics, affinity HLA peptidomics, name few. platform explored. Here, demonstrate adapted perform LC-MS-based repertoires. In side-by-side comparison extracted serum qualitatively quantitatively, whereby particular sensitivity excels. Future incorporation advanced top-down capabilities on very valuable thus also personalized

Язык: Английский

---

Flow Rate Determination of the Nanoflow Sheath Liquid CE–MS‐Coupling Applying the nanoCEasy Interface

Electrophoresis, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

ABSTRACT In recent years, nanoflow sheath liquid (nanoSL) interfaces have been used more commonly for capillary electrophoresis–mass spectrometry (CE–MS) coupling due to their high sensitivity combined with flexibility in CE separation conditions. So far, the exact amount of (SL) and, thus, dilution effect remain unknown self‐supplying type nanoSL interfaces. To quantify SL flow rates, we present here an approach determination rate based on isotopically labeled standards using nanoCEasy interface. and pumped are spiked atrazine d5‐atrazine, respectively, enabling total different electrospray (ES) Generally, rates increase higher ES voltages. Only at voltages, larger emitter sizes lead rates; low independent size. Additionally, smaller can generally be operated lower Visualizing ES, a spray angle. Higher may decrease signal intensity by diluting CE‐separated analytes. Indeed, this is observed flow‐injected analytes CE–MS analysis amino acid standard mix under aqueous acidic Therefore, preferred electroosmotic (EOF) applications. However, EOF applications, voltages required prevent accumulation background electrolyte (BGE) tip, which otherwise leads peak broadening inefficient ionization. Overall, presented data enable selection stable sensitive settings

Язык: Английский

---

CE-MS and CE-MS/MS for the Multiattribute Analysis of Monoclonal Antibody Variants at the Subunit Level

Journal of Pharmaceutical and Biomedical Analysis, Год журнала: 2024, Номер 252, С. 116495 - 116495

Опубликована: Окт. 2, 2024

Язык: Английский

---