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Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis
Author(s) -
Urlaub Jonas,
Kaiser Reinhard P.,
ScherfClavel Oliver,
Bolm Carsten,
Holzgrabe Ulrike
Publication year - 2021
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.202000307
Subject(s) - ibuprofen , enantiomer , chemistry , chromatography , capillary electrophoresis , electrolyte , detection limit , chiral resolution , oxalate , magnesium , analytical chemistry (journal) , stereochemistry , inorganic chemistry , organic chemistry , electrode , medicine , pharmacology
Besides the racemate, the S ‐enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S ‐Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg 2+ , Ca 2+ , or Zn 2+ ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 μm fused‐silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis‐(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TM‐β‐CD) as chiral selector. The quantification of R ‐Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68–5.49% R ‐Ibu (R 2 = 0.999), recovery was found to range between 97 and 103%, the RSD of intra‐ and interday precision below 2.5%, and the limit of quantification for R ‐ in S ‐Ibu was calculated to be 0.21% (extrapolated) and 0.15% (dilution of racemic ibuprofen), respectively. Isomerization of S ‐Ibu was observed under basic conditions by applying long milling times and high milling frequencies.