Multiple heart-cutting two dimensional liquid chromatography mass spectrometry: Towards real time determination of related impurities of bio-pharmaceuticals in salt based separation methods

Petersson, Patrik; Haselmann, Kim F.; Buckenmaier, Stephan

doi:10.1016/j.chroma.2016.09.023

Cited by 39 publications

(34 citation statements)

References 18 publications

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“…The 2D LC/MS technique overcomes the drawbacks of incompatibility between non‐volatile salt mobile phase and the ionization process in mass spectrometry. TOF MS is able to characterize minor complex structural components at trace levels due to its high sensitivity, efficiency and selectivity . In this article, trap‐free 2D LC coupled to IT‐TOF MS has been applied to separate and identify the components and impurities in josamycin.…”

Section: Introductionmentioning

confidence: 89%

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Characterization of a new component and impurities in josamycin by trap‐free two‐dimensional liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry

Liu

Sang

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale The toxicities of the impurities of a drug will affect the clinical effects and cause potential health risk; therefore, it is essential to study profiles of the impurities. In this study, a new structural type of component and two acid degradation impurities in josamycin were discovered and characterized for the further improvement of official monographs in pharmacopoeias. Methods The component and acid degradation impurities in josamycin were separated and preliminary characterized by trap‐free two‐dimensional liquid chromatography coupled to high‐resolution ion trap time‐of‐flight mass spectrometry (2D LC/IT‐TOF MS) in both positive and negative electrospray ionization mode. The eluent of each peak from the first dimensional chromatographic system was trapped by a switching valve and subsequently transferred to the second dimensional chromatographic system, which was connected to the mass spectrometer. Full scan MS was firstly conducted to obtain the exact m/z values of the molecules. Then LC/MS/MS and LC/MS/MS/MS experiments were performed on the compounds of interest. Results A new structural type of component, which was named as josamycin A, and two acid degradation impuritiess, which were identified as impurity I and impurity II, were discovered in josamycin. Their structures and fragmentation pattern were deduced according to MSn data. Furthermore, josamycin A was synthesized and impurity I was separated by preparative HPLC. The structures of josamycin A and the impurities were confirmed by 1H NMR and 13C NMR data. Conclusions Josamycin A was produced when the hydroxyl group on the macrolide of josamycin was oxidized into a carbonyl group. Impurity I and impurity II were produced by the loss of one molecule of acetyl mycaminose from josamycin and josamycin A, respectively. Compared with josamycin, the experimental results showed that josamycin A had a higher antibacterial activity with similar cytotoxicity, while impurity I had no antibacterial activity but a higher cytotoxicity. As a result, the control of impurity I is significant.

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Section: Introductionmentioning

confidence: 89%

“…TOF MS is able to characterize minor complex structural components at trace levels due to its high sensitivity, efficiency and selectivity. [20][21][22] In this article, trap-free 2D LC coupled to IT-TOF MS has been applied to separate and identify the components and impurities in josamycin.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a new component and impurities in josamycin by trap‐free two‐dimensional liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry

Liu

Sang

et al. 2019

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

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“…Williams and coworkers report an automated 2D‐LC method for characterization of protein aggregation with an in‐line fraction collection device (Sandra, Steenbeke, Vandenheede, Vanhoenacker, & Sandra, 2017). In certain instances, the technology has been coupled with mass spectrometers for further characteristic understanding of the chromatographic peaks (Petersson, Haselmann, & Buckenmaier, 2016; Stoll, Danforth, Zhang, & Beck, 2016). In summary, on‐line chromatography and 2D‐LC MAC systems show great promise as on‐line PAT tools for multiple CQA monitoring in bioprocesses (Figure 4).…”

Section: Process Analytical Technologiesmentioning

confidence: 99%

Technology outlook for real‐time quality attribute and process parameter monitoring in biopharmaceutical development—A review

Wasalathanthri

Rehmann

Song

et al. 2020

Biotech & Bioengineering

101

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Real‐time monitoring of bioprocesses by the integration of analytics at critical unit operations is one of the paramount necessities for quality by design manufacturing and real‐time release (RTR) of biopharmaceuticals. A well‐defined process analytical technology (PAT) roadmap enables the monitoring of critical process parameters and quality attributes at appropriate unit operations to develop an analytical paradigm that is capable of providing real‐time data. We believe a comprehensive PAT roadmap should entail not only integration of analytical tools into the bioprocess but also should address automated‐data piping, analysis, aggregation, visualization, and smart utility of data for advanced‐data analytics such as machine and deep learning for holistic process understanding. In this review, we discuss a broad spectrum of PAT technologies spanning from vibrational spectroscopy, multivariate data analysis, multiattribute chromatography, mass spectrometry, sensors, and automated‐sampling technologies. We also provide insights, based on our experience in clinical and commercial manufacturing, into data automation, data visualization, and smart utility of data for advanced‐analytics in PAT. This review is catered for a broad audience, including those new to the field to those well versed in applying these technologies. The article is also intended to give some insight into the strategies we have undertaken to implement PAT tools in biologics process development with the vision of realizing RTR testing in biomanufacturing and to meet regulatory expectations.

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“…Recently, several kinds of modulators have been developed to overcome the incompatibility problem [5]. Some of them are based on the modification of the modulator configuration like the Fixed Solvent Modulator (FSM) developed by Petersson et al [6] or the Active Solvent Modulation (ASM) proposed by Stoll et al [7,8].…”

Section: Introductionmentioning

confidence: 99%

Application of the new at-column dilution (ACD) modulator for the two-dimensional RP×HILIC analysis of Buddleja davidii

et al. 2020

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The focus of this study was the analysis of the complex chemical composition from different parts of Buddleja davidii, whose species are commonly known as ornamental plants and herbal medicines in many countries. As an herbal medicine, it has been utilized for stroke treatments, headache, wound healing, neurological disorder, etc. However, the understanding of its chemical matrices is still insufficient. Therefore, an online two-dimensional reversed phase liquid chromatography x hydrophilic interaction liquid chromatography (RPLCxHILIC) system coupled with mass spectrometry was applied for further detailed investigation of the chemical constituents in Buddleja dividii. In this two-dimensional liquid chromatography (2D-LC) method, a new atcolumn dilution (ACD) modulator was introduced in the 2D-LC system to solve the incompatibility problem of the mobile phase between two dimensions, which resulted in a 2D-LC analysis with high orthogonality. For the root extract, as one of the analyzed samples, the optimization of the 1 D and 2 D gradients was carried out carefully. With this new modulator, much better peak separation and better peak shape were achieved compared to two-dimensional liquid chromatography system using a traditional standard (TS) modulator. With a similar approach, the other four parts of Buddleja davidii were well separated. Comparing the different analyzed parts, flowers and leaves showed the most complex profiles. MS and MS/MS data were obtained successfully, which demonstrated the potential of the proposed RPLCxHILIC-MS system in the constituents' analysis of herbal medicine. However, due to the lack of reported reference information, 24 compounds could be tentatively identified.

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Multiple heart-cutting two dimensional liquid chromatography mass spectrometry: Towards real time determination of related impurities of bio-pharmaceuticals in salt based separation methods

Cited by 39 publications

References 18 publications

Characterization of a new component and impurities in josamycin by trap‐free two‐dimensional liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry

Characterization of a new component and impurities in josamycin by trap‐free two‐dimensional liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry

Technology outlook for real‐time quality attribute and process parameter monitoring in biopharmaceutical development—A review

Application of the new at-column dilution (ACD) modulator for the two-dimensional RP×HILIC analysis of Buddleja davidii

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