Vinyl and methyl-ester groups in the insoluble polymer drug patiromer identified and quantified by solid-state NMR.
J Pharm Biomed Anal
; 246: 116228, 2024 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-38781726
ABSTRACT
Patiromer (Veltassa®) is a crosslinked, insoluble co-polymer drug used as a nonabsorbent potassium binder, approved for treatment of hyperkalemia. Quantitative solid-state 13C nuclear magnetic resonance (NMR) analysis with comprehensive peak assignment, component quantification, and calculation of mole and weight fractions of monomer units was performed on three doses of patiromer. The workflow is documented in detail. Spectrally edited solid-state 13C NMR spectra of patiromer show =CHn peaks of matching intensity at 116 and 141â¯ppm, characteristic of -CH=CH2 vinyl groups. Similar spectral features can be observed in earlier studies but were previously ignored. In this study, the vinyl signals are well-resolved in a 2-s direct polarization (DP) spectrum without and with dipolar dephasing, which confirms that these sp2-hybridized carbons are bonded to hydrogen and partially mobile, consistent with vinyl side groups from incompletely reacted divinyl crosslinkers. The vinyl groups account for 1.6% of all carbon, 3% of the monomer units, and nearly 1/3 of the crosslinkers. Furthermore, an unexpected OCH3 moiety accounting for â¼1.2% of all carbons was identified by spectral editing; its chemical shift of 54â¯ppm is more consistent with a methyl ester than with a methyl ether. It can originate from incomplete hydrolysis of â¼6% of methyl-2-fluoroacrylate, the main monomer of patiromer. Characteristic cross peaks in two-dimensional 1H-13C heteronuclear correlation NMR confirm the presence of the vinyl and OCH3 groups. Trace amounts of xanthan gum are also detected. The quantitative 13C NMR spectrum of patiromer has been matched in a simulation using a model with five monomer units.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Espectroscopia de Ressonância Magnética
/
Ésteres
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos