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Simultaneous enantioseparation of a basic drug compound and its acidic intermediate by capillary electrophoresis
Author(s) -
Zhou Lili,
Thompson Richard,
French Mike,
Ellison Dean,
Wyvratt Jean
Publication year - 2002
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/1615-9314(20021101)25:15/17<1183::aid-jssc1183>3.0.co;2-s
Subject(s) - chemistry , capillary electrophoresis , enantiomer , chromatography , reagent , selectivity , matrix (chemical analysis) , stereochemistry , organic chemistry , catalysis
The simultaneous enantioseparation of a basic drug compound, 2( R )‐ N ‐[1‐(6‐aminopyridin‐2‐ylmethyl)piperidin‐4‐yl]‐2‐[(1 R )‐3,3‐difluorocyclopentyl]‐2‐hydroxy‐2‐phenylacetamide (M3), and its chiral acidic intermediate, ( R , R ) 1‐(2,2‐difluorocyclopentyl)phenylacetic acid (MA), was investigated by capillary electrophoresis (CE) with various cyclodextrins (CDs). After an initial screening, a single‐isomer CD, octakis(2,3‐diacetyl‐6‐sulfo)‐gamma‐CD (ODAS‐γ‐CD), was selected for further method development based on separation selectivity and the peak migration time. Other method parameters such as pH of background electrolyte (BGE), type of capillary, temperature, and organic modifier were varied in order to optimize the method. The optimal method was validated in terms of linearity, sensitivity, precision, ruggedness, and specificity. A mixture of enantiomers of M3 and MA were spiked into a matrix of reagents used for the synthetic step and the resulting solution was evaluated by the optimized CE‐chiral method. The results indicate both pairs of M3 and MA enantiomers were free of interference from the reaction matrix. Therefore, the feasibility of utilizing the method to monitor possible enantio‐conversion during the synthetic process was demonstrated.