{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:14:02Z","timestamp":1790093642697,"version":"4.0.1"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"37","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["EP\/Y002423\/1"],"award-info":[{"award-number":["EP\/Y002423\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000837","name":"University of Nottingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pentosan polysulfate sodium (PPS) is a glycosaminoglycan mimic that is the only current active pharmaceutical ingredient (API) for the oral treatment of interstitial cystitis. PPS is an inherently complex API due to variations in chain length, backbone structure, sulfation pattern, and end group, making discriminating between batch-to-batch as well as manufacturer-to-manufacturer differences difficult. In this study, high-throughput liquid handling and time-of-flight secondary-ion mass spectrometry (ToF-SIMS) are used to enable the rapid chemical analysis (450 samples in 6 h) of small amounts (&amp;lt;150 ng) of PPS. Chemical discrimination between PPS produced by different manufacturers and, in one case, batch-to-batch variation of the same manufacturer were achieved. Analysis of samples using an OrbiSIMS instrument is used to provide confident, putative assignment of the discriminating ions to enable structural interpretation of the variance observed between samples. Together with analysis of samples spiked with NaSO4, free sulfate, degree of sulfation along with the sulfate pattern are implicated as key differences between manufacturers\/batches. This approach is likely to be highly beneficial for the rapid quality control of PPS.<\/jats:p>","DOI":"10.1021\/acsomega.6c05275","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:01:15Z","timestamp":1789027275000},"page":"55786-55796","source":"Crossref","is-referenced-by-count":0,"title":["Secondary-Ion Mass\nSpectrometry Analysis of Pentosan\nPolysulfate"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7756-8444","authenticated-orcid":true,"given":"Andrew L.","family":"Hook","sequence":"first","affiliation":[{"name":"University of Nottingham , , ,","place":["Nottingham, U.K., NG7 2RD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Kotowska","sequence":"additional","affiliation":[{"name":"University of Nottingham , , ,","place":["Nottingham, U.K., NG7 2RD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw E. L.","family":"Williams","sequence":"additional","affiliation":[{"name":"University of Nottingham , , ,","place":["Nottingham, U.K., NG7 2RD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Wondraczek","sequence":"additional","affiliation":[{"name":"HV-Polysaccharides GmbH & Co. KG , Am Amselberg 1 , ,","place":["Bucha, Germany, 07751"]},{"name":"Fraunhofer Center for Chemical-Biotechnological Processes CBP , Am Haupttor (Gate 12, Building 1251) , ,","place":["Leuna, Germany, 06237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"issue":"6","key":"2026092210572585800_cit1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.2165\/00003495-200666060-00006","article-title":"Pentosan polysulfate: A review of its use in the relief\nof bladder pain or discomfort in interstitial cystitis","volume":"66","author":"Anderson","year":"2006","journal-title":"Drugs"},{"issue":"6","key":"2026092210572585800_cit2","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/0090-4295(90)80116-5","article-title":"Pentosan\npolysulfate sodium for therapy of interstitial cystitis: a double-blind\nplacebo-controlled clinical-study","volume":"35","author":"Mulholland","year":"1990","journal-title":"Urology"},{"issue":"1","key":"2026092210572585800_cit3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-62041-y","article-title":"Screening practices and risk assessment for maculopathy\nin pentosan polysulfate users across different exposure levels","volume":"14","author":"Kwon","year":"2024","journal-title":"Sci. Rep."},{"issue":"4","key":"2026092210572585800_cit4","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1097\/01.ju.0000159198.83103.01","article-title":"Pentosan polysulfate\nsodium therapy for men with chronic pelvic pain syndrome: A multicenter,\nrandomized, placebo controlled study","volume":"173","author":"Nickel","year":"2005","journal-title":"J. Urol."},{"issue":"1","key":"2026092210572585800_cit5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054459","article-title":"Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses","volume":"8","author":"Schuchman","year":"2013","journal-title":"PLoS One"},{"issue":"5","key":"2026092210572585800_cit6","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1111\/fcp.12781","article-title":"Pentosan\npolysulfate exerts anti-inflammatory\neffect and halts albuminuria progression in diabetic nephropathy:\nRole of combined losartan","volume":"36","author":"Eita","year":"2022","journal-title":"Fundam. Clin. Pharmacol."},{"issue":"10","key":"2026092210572585800_cit7","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1038\/labinvest.2011.93","article-title":"Inhibition of inflammation\nby pentosan polysulfate impedes the development\nand progression of severe diabetic nephropathy in aging C57B6 mice","volume":"91","author":"Wu","year":"2011","journal-title":"Lab. Invest."},{"key":"2026092210572585800_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113867","article-title":"Pentosan polysulfate\nto control hepcidin expression in vitro and in vivo","volume":"175","author":"Asperti","year":"2020","journal-title":"Biochem. Pharmacol."},{"issue":"22","key":"2026092210572585800_cit9","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1093\/jnci\/84.22.1716","article-title":"Inhibition\nby pentosan polysulfate\n(PPS) of heparin-binding growth-factors released from tumor-cells\nand blockage by PPS of tumor-growth in animals","volume":"84","author":"Zugmaier","year":"1992","journal-title":"J. Natl. Cancer Inst."},{"issue":"15","key":"2026092210572585800_cit10","doi-asserted-by":"publisher","first-page":"8063","DOI":"10.1128\/JVI.00224-15","article-title":"Pentosan Polysulfate:\na Novel Glycosaminoglycan-Like\nMolecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction\nand Inflammatory Disease","volume":"89","author":"Herrero","year":"2015","journal-title":"J. Virol."},{"issue":"6","key":"2026092210572585800_cit11","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1055\/a-1807-0168","article-title":"Pentosan Polysulfate Inhibits Attachment and Infection\nby SARS-CoV-2 In Vitro: Insights into Structural Requirements for\nBinding","volume":"122","author":"Bertini","year":"2022","journal-title":"Thromb. Haemostasis"},{"issue":"1","key":"2026092210572585800_cit12","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10010049","article-title":"Enoxaparin and Pentosan\nPolysulfate Bind to the SARS-CoV-2\nSpike Protein and Human ACE2 Receptor, Inhibiting Vero Cell Infection","volume":"10","author":"Ennemoser","year":"2022","journal-title":"Biomedicines"},{"issue":"2","key":"2026092210572585800_cit13","doi-asserted-by":"publisher","DOI":"10.3390\/ph15020258","article-title":"Potential\nAnti-SARS-CoV-2 Activity of Pentosan Polysulfate and Mucopolysaccharide\nPolysulfate","volume":"15","author":"Zhang","year":"2022","journal-title":"Pharmaceuticals"},{"key":"2026092210572585800_cit14","first-page":"325","article-title":"Xylans\nof industrial and biomedical importance","volume-title":"Biotechnology and Genetic Engineering Reviews","author":"Ebringerova","year":"1999"},{"issue":"3","key":"2026092210572585800_cit15","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1021\/bm010062x","article-title":"Distribution of uronic acids in xylans\nfrom various species of soft- and hardwood as determined by MALDI\nmass spectrometry","volume":"2","author":"Jacobs","year":"2001","journal-title":"Biomacromolecules"},{"key":"2026092210572585800_cit16","unstructured":"De Ferra, L.; Naggi, A.; Zenoni, M.; Pinto, B.\n          Method for the qualification of preparations\nof pentosan polysulfate, raw materials and production processes thereof. A1WO 2014114723.2014."},{"issue":"6","key":"2026092210572585800_cit17","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1002\/mame.201000390","article-title":"Homogeneous\nSulfation of Xylan from\nDifferent Sources","volume":"296","author":"Daus","year":"2011","journal-title":"Macromol. Mater. Eng."},{"issue":"2","key":"2026092210572585800_cit18","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/0144-8617(91)90104-K","article-title":"Pyridinium substitution during the\nsulfation of polysaccharides in the presence of pyridine","volume":"16","author":"Ahrgren","year":"1991","journal-title":"Carbohydr. Polym."},{"key":"2026092210572585800_cit19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.carbpol.2018.10.119","article-title":"Synthesis of pyridine-free\nxylan sulfates","volume":"206","author":"Pfeifer","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"2026092210572585800_cit20","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2020.115913","article-title":"In-depth structural\ncharacterization of pentosan polysulfate\nsodium complex drug using orthogonal analytical tools","volume":"234","author":"Alekseeva","year":"2020","journal-title":"Carbohydr. Polym."},{"issue":"3","key":"2026092210572585800_cit21","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-023-00815-4","article-title":"A Precise qNMR Method\nfor the Rapid Quantification of Lot-to-Lot Variations in Multiple\nQuality Attributes of Pentosan Polysulfate Sodium","volume":"25","author":"Wang","year":"2023","journal-title":"AAPS J."},{"key":"2026092210572585800_cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.114589","article-title":"2D NMR peak\nprofiling to compare chemical differences between batches of pentosan\npolysulfate sodium","volume":"211","author":"Chen","year":"2022","journal-title":"J. Pharm. Biomed. Anal."},{"key":"2026092210572585800_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2023.121201","article-title":"Chemical and\nbiological differences between original and mimetic\npentosan polysulfates","volume":"319","author":"Lenhart","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"2026092210572585800_cit24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2023.115672","article-title":"Further advances in\nidentification of pentosan polysulfate monosaccharide composition\nby NMR","volume":"235","author":"Eisele","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"14","key":"2026092210572585800_cit25","doi-asserted-by":"publisher","first-page":"3334","DOI":"10.1021\/ie020596u","article-title":"Within-Batch\nand Batch-to-Batch Inferential-Adaptive\nControl of Semibatch Reactors: A Partial Least Squares Approach","volume":"42","author":"Flores-Cerrillo","year":"2003","journal-title":"Ind. Eng. Chem. Res."},{"issue":"1","key":"2026092210572585800_cit26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42004-021-00506-1","article-title":"High\nsensitivity analysis of nanogram quantities of glycosaminoglycans\nusing ToF-SIMS","volume":"4","author":"Hook","year":"2021","journal-title":"Commun. Chem."},{"key":"2026092210572585800_cit27","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2025.124415","article-title":"Validation\nof the use of ToF-SIMS for analysis of glycosaminoglycans","volume":"371","author":"Milne","year":"2026","journal-title":"Carbohydr. Polym."},{"issue":"12","key":"2026092210572585800_cit28","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1038\/nmeth.4504","article-title":"The 3D OrbiSIMS-label-free\nmetabolic imaging\nwith subcellular lateral resolution and high mass-resolving power","volume":"14","author":"Passarelli","year":"2017","journal-title":"Nat. Methods"},{"issue":"3","key":"2026092210572585800_cit29","doi-asserted-by":"publisher","DOI":"10.1116\/6.0002604","article-title":"Identification\nof Pseudomonas aeruginosa exopolysaccharide Psl in biofilms using\n3D OrbiSIMS","volume":"18","author":"Khateb","year":"2023","journal-title":"Biointerphases"},{"issue":"45","key":"2026092210572585800_cit30","doi-asserted-by":"publisher","first-page":"38739","DOI":"10.1021\/acsami.8b12473","article-title":"High-Throughput\nAssessment and Modeling of a Polymer Library Regulating Human Dental\nPulp-Derived Stem Cell Behavior","volume":"10","author":"Rasi Ghaemi","year":"2018","journal-title":"ACS Appl. Mater.\nInterfaces"},{"key":"2026092210572585800_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120312","article-title":"Discovery of hemocompatible bacterial biofilm-resistant\ncopolymers","volume":"260","author":"Singh","year":"2020","journal-title":"Biomaterials"},{"issue":"8","key":"2026092210572585800_cit32","doi-asserted-by":"publisher","DOI":"10.1002\/mame.201800146","article-title":"High-Throughput Miniaturized\nScreening of Nanoparticle Formation via Inkjet Printing","volume":"303","author":"Styliari","year":"2018","journal-title":"Macromol. Mater. Eng."},{"issue":"3","key":"2026092210572585800_cit33","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nm0302-295","article-title":"Autoantigen microarrays for multiplex\ncharacterization of autoantibody responses","volume":"8","author":"Robinson","year":"2002","journal-title":"Nat. Med."},{"issue":"1","key":"2026092210572585800_cit34","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/0003-9861(88)90437-7","article-title":"Binding of calcium to glycosaminoglycans:\nAn equilibrium dialysis study","volume":"260","author":"Hunter","year":"1988","journal-title":"Arch. Biochem.\nBiophys."},{"key":"2026092210572585800_cit35","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0531-5131(01)00458-7","article-title":"Binding between\ncalcium\nions and chondroitin sulfate chains of salmon nasal cartilage glycosaminoglycan","volume":"1223","author":"Uchisawa","year":"2001","journal-title":"Int. Congr. Ser."},{"issue":"6","key":"2026092210572585800_cit36","first-page":"484","article-title":"Stromal sodium binding\nafter glycosaminoglycan\ndigestion","volume":"15","author":"Green","year":"1976","journal-title":"Invest. Ophthalmol. Visual Sci."},{"issue":"4","key":"2026092210572585800_cit37","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1021\/jasms.4c00494","article-title":"The Impact of the Mass Analyzer and\nTissue Section Thickness on Spatial N-Glycomics with MALDI-MSI","volume":"36","author":"Velic\u030ckovic\u0301","year":"2025","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"5","key":"2026092210572585800_cit38","doi-asserted-by":"publisher","DOI":"10.1116\/6.0003821","article-title":"OrbiSIMS depth profiling\nof semiconductor materials\u2500Useful\nyield and depth resolution","volume":"42","author":"Zhou","year":"2024","journal-title":"J. Vac. Sci. Technol.,\nA"},{"issue":"4","key":"2026092210572585800_cit39","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s10822-018-0106-1","article-title":"Sparse\nQSAR modelling methods for therapeutic and regenerative medicine","volume":"32","author":"Winkler","year":"2018","journal-title":"J. Comput.-Aided Mol. Des."},{"issue":"1","key":"2026092210572585800_cit40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48694-3","article-title":"Integrating cryo-OrbiSIMS\nwith computational modelling and metadynamics simulations enhances\nRNA structure prediction at atomic resolution","volume":"15","author":"Ward","year":"2024","journal-title":"Nat. Commun."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c05275","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/37\/55786\/68467461\/acsomega.6c05275.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/37\/55786\/68467461\/acsomega.6c05275.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:50:24Z","timestamp":1790092224000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/37\/55786\/5427450\/Secondary-Ion-Mass-Spectrometry-Analysis-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":40,"journal-issue":{"issue":"37","published-online":{"date-parts":[[2026,9,10]]},"published-print":{"date-parts":[[2026,9,22]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c05275","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}