Multi-dimensional plug-and-play liquid chromatography-native ion mobility mass spectrometry method for the analysis of biotherapeutics

Jia, Mengxuan; Mozziconacci, Olivier; Abend, Andreas; Wuelfing, W. Peter; Pennington, Justin

doi:10.1016/j.ijms.2021.116725

Cited by 9 publications

(3 citation statements)

References 50 publications

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“…The present study demonstrates the challenges in distinguishing and characterizing similar HMW size variants in antibody co-formulations. The trastuzumab/pertuzumab co-formulation aggregate assessment represents a most demanding example, adding value to other recent studies with less related co-formulated antibody products. , The presented data verify the high stability of the trastuzumab/pertuzumab co-formulation where only minor aggregate formation is observed with product storage and accelerated temperature conditions (below 1%).…”

Section: Discussionsupporting

confidence: 69%

Identification of Hetero-aggregates in Antibody Co-formulations by Multi-dimensional Liquid Chromatography Coupled to Mass Spectrometry

et al. 2023

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Antibody combination therapies have become viable therapeutic treatment options for certain severe diseases such as cancer. The co-formulation production approach is intrinsically associated with more complex drug product variant profiles and creates more challenges for analytical control of drug product quality. In addition to various individual quality attributes, those arising from the interactions between the antibodies also potentially emerge through co-formulation. In this study, we describe the development of a widely applicable multi-dimensional liquid chromatography coupled to tandem mass spectrometry method for antibody homo-versus hetero-aggregate characterization. The co-formulation of trastuzumab and pertuzumab was used, a challenging model system, comprising two monoclonal antibodies with very similar physicochemical properties. The data presented demonstrate the high stability of the co-formulation, where only minor aggregate formation is observed upon product storage and accelerated temperature or light-stress conditions. The results also show that the homo-and hetero-aggregates, formed in low and comparable proportions, are only marginally impacted by the formulation and product storage conditions. No preferential formation of hetero-aggregates, in comparison to the already existing pertuzumab and trastuzumab homo-aggregates, was observed.

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Section: Discussionsupporting

confidence: 69%

Identification of Hetero-aggregates in Antibody Co-formulations by Multi-dimensional Liquid Chromatography Coupled to Mass Spectrometry

et al. 2023

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“…Hybrid methods that combine different modes of separation and detection will be particularly useful. Such methods (e.g., SEC-MS, EC-IEX-MS or cIEF-MS) [122][123][124] are already emerging and can be very valuable during the development of coformulated antibodies.…”

Section: Discussionmentioning

confidence: 99%

It is Never Too Late for a Cocktail - Development and Analytical Characterization of Fixed-dose Antibody Combinations

Krieg

Winter

Svilenov

2022

Journal of Pharmaceutical Sciences

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“…The resulting SEC-IEX-UV-nMS offered detection via UV absorbance and mass detection in a single method. This approach has been successfully applied for analyzing a significant spectrum of biologics and biotherapeutics, to separate growth hormones, oligomer state distributions of liraglutides in solutions with different pHs (34), and native states of homodimers and heterodimers of force stressed studies of mAb mixtures (35). Researchers have indicated that by applying an external isocratic flow pump on a simple binary pump, any binary LC system can be transformed into a simple multi-dimensional analytical tool (35).…”

Section: Informatics For Your Lab -Lims • Eln • Les • Sdmsmentioning

confidence: 99%

Acid-Catalyzed Isomerization of Carbonyls-2,4- dinitrophenylhydrazone in Mainstream Smoke of Heat-Not-Burn Tobacco Product for HPLC Analysis

Zhang

Zhu

et al. 2022

LCGC N. Am.

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Carbonyls (such as acrolein, acetaldehyde, and formaldehyde) are the critical type of carcinogens and toxicants contained within the heat-not-burn (HNB) tobacco products. Using HNB products can have negative effects on human health; therefore, it is important to measure carbonyl contents within the HNB mainstream smoke. Typically, the 2,4-dinitrophenylhydrazine (DNPH) approach involves forming the 2,4-dinitrophenylhydrazone derivatives, which is the most extensively adopted approach to qualitatively and quantitatively analyze carbonyl compounds. However, the approach can result in analytical error because 2,4-dinitrophenylhydrazones contains the E-stereoisomer as well as the Z-stereoisomer. Only an E-isomers exists in the purified carbonyls-2,4-dinitrophenylhydrazone, but when acid is added, the E-isomer and Z-isomer can be observed. For propionaldehyde-, acetaldehyde-, crotonaldehyde-, acrolein-, and 2-butanone-2,4-dinitrophenylhydrazones, their equilibrium Z/E isomer ratios are 0.143, 0.309, 0.093, 0.028, and 0.154. In the case of adding trace water into hydrazone derivatives dissolved within the acetonitrile solution, the derivative contents decrease, whereas the free DNPH content increases. Therefore, catalytic acid should be added in the low content. To determine carbonyls-2,4-dinitrophenylhydrazones through HPLC, the optimal approach is adding phosphoric acid into the samples and the standard reference solution to form the 0.02–1.0% acid solution.

show abstract

Multi-dimensional plug-and-play liquid chromatography-native ion mobility mass spectrometry method for the analysis of biotherapeutics

Cited by 9 publications

References 50 publications

Identification of Hetero-aggregates in Antibody Co-formulations by Multi-dimensional Liquid Chromatography Coupled to Mass Spectrometry

Identification of Hetero-aggregates in Antibody Co-formulations by Multi-dimensional Liquid Chromatography Coupled to Mass Spectrometry

It is Never Too Late for a Cocktail - Development and Analytical Characterization of Fixed-dose Antibody Combinations

Acid-Catalyzed Isomerization of Carbonyls-2,4- dinitrophenylhydrazone in Mainstream Smoke of Heat-Not-Burn Tobacco Product for HPLC Analysis

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