Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

Shi-Qi Wang; Xun Zhao; Li-Jun Zhang; Yue-Mei Zhao; Lei Chen; Jin-Lin Zhang; Bao-Cheng Wang; Sheng Tang; Tom Yuan; Yaozuo Yuan; Mei Zhang; Hian Kee Lee; Hai-Wei Shi

doi:10.1016/j.jpha.2023.12.019

Volume 14 Issue 5

May 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(5): 100929

Shi-Qi Wang, Xun Zhao, Li-Jun Zhang, Yue-Mei Zhao, Lei Chen, Jin-Lin Zhang, Bao-Cheng Wang, Sheng Tang, Tom Yuan, Yaozuo Yuan, Mei Zhang, Hian Kee Lee, Hai-Wei Shi. Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100929. doi: 10.1016/j.jpha.2023.12.019

Citation:

Shi-Qi Wang, Xun Zhao, Li-Jun Zhang, Yue-Mei Zhao, Lei Chen, Jin-Lin Zhang, Bao-Cheng Wang, Sheng Tang, Tom Yuan, Yaozuo Yuan, Mei Zhang, Hian Kee Lee, Hai-Wei Shi. Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100929. doi: 10.1016/j.jpha.2023.12.019

Citation:

Shi-Qi Wang, Xun Zhao, Li-Jun Zhang, Yue-Mei Zhao, Lei Chen, Jin-Lin Zhang, Bao-Cheng Wang, Sheng Tang, Tom Yuan, Yaozuo Yuan, Mei Zhang, Hian Kee Lee, Hai-Wei Shi. Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100929. doi: 10.1016/j.jpha.2023.12.019

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Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

doi: 10.1016/j.jpha.2023.12.019

Shi-Qi Wang^a,b,
Xun Zhao^a,
Li-Jun Zhang^a,b,
Yue-Mei Zhao^a,c,
Lei Chen^d,
Jin-Lin Zhang^a,
Bao-Cheng Wang^{e
,
,},
Sheng Tang^f,
Tom Yuan^g,
Yaozuo Yuan^{a
,
,},
Mei Zhang^a,
Hian Kee Lee^{f,h
,
,},
Hai-Wei Shi^{a
,
,}

a. Jiangsu Institute for Food and Drug Control, Nanjing, 210019, China;
b. School of Pharmacy, China Pharmaceutical University, Nanjing, 211112, China;
c. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210046, China;
d. Chinese Pharmacopoeia Commission, Beijing, 100061, China;
e. Nanjing Well Pharmaceutical Group Co., Ltd., Nanjing, 210018, China;
f. School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu, 212003, China;
g. University of Massachusetts Amherst, Amherst, 01003, USA;
h. Department of Chemistry, National University of Singapore, Singapore, 117543, Singapore

Funds:

The authors are grateful for the financial support from the Science Research Program Project for Drug Regulation, Jiangsu Drug Administration, China (Grant No.: 202207), the National Drug Standards Revision Project, China (Grant No.: 2023Y41), the National Natural Science Foundation of China (Grant No.: 22276080), and the Foreign Expert Project, China (Grant No.: G2022014096L).

Received Date: Sep. 14, 2023
Accepted Date: Dec. 28, 2023
Rev Recd Date: Nov. 27, 2023
Publish Date: May 30, 2024

Abstract

Abstract

Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.
- Polysorbate 20,
- Component,
- Database,
- Discrimination,
- Degradation

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References(40)

References

[1]	R. Muzzalupo, L. Tavano, C.O. Rossi, et al., Synthesis and properties of methacrylic-functionalized tween monomer networks, Langmuir 25 (2009) 1800-1806.
[2]	A. Raval, P. Bahadur, A. Raval, Effect of nonionic surfactants in release media on accelerated in-vitro release profile of sirolimus eluting stents with biodegradable polymeric coating, J. Pharm. Anal. 8 (2018) 45-54.
[3]	H. Kumari, S.R. Kline, J.L. Atwood, Aqueous solubilization of hydrophobic supramolecular metal-organic nanocapsules, Chem. Sci. 5 (2014) 2554-2559.
[4]	C. Caddeo, M.L. Manca, J.E. Peris, et al., Tocopherol-loaded transfersomes: in vitro antioxidant activity and efficacy in skin regeneration, Int. J. Pharm. 551 (2018) 34-41.
[5]	C. Yucel, V. Quagliariello, R.V. Iaffaioli, et al., Submicron complex lipid carriers for curcumin delivery to intestinal epithelial cells: Effect of different emulsifiers on bioaccessibility and cell uptake, Int. J. Pharm. 494 (2015) 357-369.
[6]	R. Jain, R.K. Yadav, Voltammetric behavior of sedative drug midazolam at glassy carbon electrode in solubilized systems, J. Pharm. Anal. 2 (2012) 123-129.
[7]	A. Kannan, I.C. Shieh, P.G. Negulescu, et al., Adsorption and aggregation of monoclonal antibodies at silicone oil-water interfaces, Mol. Pharmaceutics 18 (2021) 1656-1665.
[8]	A.S. Roy, A.K. Dinda, N.K. Pandey, et al., Effects of urea, metal ions and surfactants on the binding of baicalein with bovine serum albumin, J. Pharm. Anal. 6 (2016) 256-267.
[9]	A.D. Kanthe, M. Krause, S. Zheng, et al., Armoring the interface with surfactants to prevent the adsorption of monoclonal antibodies, ACS Appl. Mater. Interfaces 12 (2020) 9977-9988.
[10]	T.A. Khan, H.C. Mahler, R.S.K. Kishore, Key interactions of surfactants in therapeutic protein formulations: A review, Eur. J. Pharm. Biopharm. 97 (2015) 60-67.
[11]	J.S. Katz, Y. Tan, K. Kuppannan, et al., Amino-acid-incorporating nonionic surfactants for stabilization of protein pharmaceuticals, ACS Biomater. Sci. Eng. 2 (2016) 1093-1096.
[12]	K. Yang, A. Hewarathna, I. Geerlof-Vidavsky, et al., Screening of polysorbate-80 composition by high resolution mass spectrometry with rapid H/D exchange, Anal. Chem. 91 (2019) 14649-14656.
[13]	J.R. Snelling, C.A. Scarff, J.H. Scrivens, Characterization of complex polysorbate formulations by means of shape-selective mass spectrometry, Anal. Chem. 84 (2012) 6521-6529.
[14]	Y. Li, D. Hewitt, Y.K. Lentz, et al., Characterization and stability study of polysorbate 20 in therapeutic monoclonal antibody formulation by multidimensional ultrahigh-performance liquid chromatography-charged aerosol detection-mass spectrometry, Anal. Chem. 86 (2014) 5150-5157.
[15]	N. Doshi, B. Demeule, S. Yadav, Understanding particle formation: Solubility of free fatty acids as polysorbate 20 degradation byproducts in therapeutic monoclonal antibody formulations, Mol. Pharm. 12 (2015) 3792-3804.
[16]	D.H. Evers, T. Schultz-Fademrecht, P. Garidel, et al., Development and validation of a selective marker-based quantification of polysorbate 20 in biopharmaceutical formulations using UPLC QDa detection, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1157 (2020), 122287.
[17]	S. Dubey, R. Giovannini, Stability of biologics and the quest for polysorbate alternatives, Trends Biotechnol. 39 (2021) 546-549.
[18]	X. Li, Z. Wang, B. Zheng, et al., Novel strategy to rapidly profile and identify oxidized species of polysorbate 80 using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, Anal. Chem. 95 (2023) 9156-9163.
[19]	K. Zhang, J.D. Pellett, A.S. Narang, et al., Reactive impurities in large and small molecule pharmaceutical excipients - A review, Trac Trends Anal. Chem. 101 (2018) 34-42.
[20]	A. Tomlinson, B. Demeule, B. Lin, et al., Polysorbate 20 degradation in biopharmaceutical formulations: Quantification of free fatty acids, characterization of particulates, and insights into the degradation mechanism, Mol. Pharmaceutics 12 (2015) 3805-3815.
[21]	N. Doshi, J. Martin, A. Tomlinson, Improving prediction of free fatty acid particle formation in biopharmaceutical drug products: Incorporating ester distribution during polysorbate 20 degradation, Mol. Pharm. 17 (2020) 4354-4363.
[22]	M. Dwivedi, M. Blech, I. Presser, et al., Polysorbate degradation in biotherapeutic formulations: Identification and discussion of current root causes, Int. J. Pharm. 552 (2018) 422-436.
[23]	M. Manaargadoo-Catin, A. Ali-Cherif, J.L. Pougnas, et al., Hemolysis by surfactants: A review, Adv. Colloid Interface Sci. 228 (2016) 1-16.
[24]	J. Ye, L. Li, J. Yin, et al., Tumor-targeting intravenous lipid emulsion of paclitaxel: Characteristics, stability, toxicity, and toxicokinetics, J. Pharm. Anal. 12 (2022) 901-912.
[25]	S. Yang, J. Liu, Y. Chen, et al., Reversal effect of Tween-20 on multidrug resistance in tumor cells in vitro, Biomed. Pharmacother. 66 (2012) 187-194.
[26]	D. Hewitt, M. Alvarez, K. Robinson, et al., Mixed-mode and reversed-phase liquid chromatography-tandem mass spectrometry methodologies to study composition and base hydrolysis of polysorbate 20 and 80, J. Chromatogr. A 1218 (2011) 2138-2145.
[27]	Q. Zhang, Y. Meng, H. Yang, et al., Quantitative analysis of polysorbates 20 and 40 by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom. 27 (2013) 2777-2782.
[28]	N. Glucklich, S. Carle, J. Buske, et al., Assessing the polysorbate degradation fingerprints and kinetics of lipases - how the activity of polysorbate degrading hydrolases is influenced by the assay and assay conditions, Eur. J. Pharm. Sci. 166 (2021), 105980.
[29]	M. Dwivedi, J. Buske, F. Haemmerling, et al., Acidic and alkaline hydrolysis of polysorbates under aqueous conditions: Towards understanding polysorbate degradation in biopharmaceutical formulations, Eur. J. Pharm. Sci. 144 (2020), 105211.
[30]	J. Kim, J. Qiu, Quantitation of low concentrations of polysorbates in high protein concentration formulations by solid phase extraction and cobalt-thiocyanate derivatization, Anal. Chim. Acta 806 (2014) 144-151.
[31]	A. Martos, M. Berger, W. Kranz, et al., Novel high-throughput assay for polysorbate quantification in biopharmaceutical products by using the fluorescent dye DiI, J. Pharm. Sci. 109 (2020) 646-655.
[32]	D. Hewitt, T. Zhang, Y.H. Kao, Quantitation of polysorbate 20 in protein solutions using mixed-mode chromatography and evaporative light scattering detection, J. Chromatogr. A 1215 (2008) 156-160.
[33]	T. Diederichs, J.J. Mittag, J. Humphrey, et al., Existence of a superior polysorbate fraction in respect to protein stabilization and particle formation? Int. J. Pharm. 635 (2023), 122660.
[34]	S. Fekete, K. Ganzler, J. Fekete, Simultaneous determination of polysorbate 20 and unbound polyethylene-glycol in protein solutions using new core-shell reversed phase column and condensation nucleation light scattering detection, J. Chromatogr. A 1217 (2010) 6258-6266.
[35]	S. Lippold, S.H.S. Koshari, R. Kopf, et al., Impact of mono- and poly-ester fractions on polysorbate quantitation using mixed-mode HPLC-CAD/ELSD and the fluorescence micelle assay, J. Pharm. Biomed. Anal. 132 (2017) 24-34.
[36]	X. Zhou, X. Meng, L. Cheng, et al., Development and application of an MSALL-based approach for the quantitative analysis of linear polyethylene glycols in rat plasma by liquid chromatography triple-quadrupole/time-of-flight mass spectrometry, Anal. Chem. 89 (2017) 5193-5200.
[37]	Z. Wang, Y. Wang, C. Tie, et al., A fast strategy for profiling and identifying pharmaceutic excipient polysorbates by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry, J. Chromatogr. A 1609 (2020), 460450.
[38]	O.V. Borisov, J.A. Ji, Y.J. Wang, et al., Toward understanding molecular heterogeneity of polysorbates by application of liquid chromatography-mass spectrometry with computer-aided data analysis, Anal. Chem. 83 (2011) 3934-3942.
[39]	T. Vehovec, A. Obreza, Review of operating principle and applications of the charged aerosol detector, J. Chromatogr. A 1217 (2010) 1549-1556.
[40]	Q. Xu, S. Tan, Quantitative analysis of 3-isopropylamino-1, 2-propanediol as a degradation product of metoprolol in pharmaceutical dosage forms by HILIC-CAD, J. Pharm. Anal. 9 (2019) 431-436.