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Separation and preparative purification of l ‐ and d ‐valine ester: Diastereomeric conjugates of atazanavir using a combination of 2‐propanol and acetonitrile in reversed‐phase high‐performance liquid chromatography
Author(s) -
Shyamsundar Murugesan,
Chauthe Siddheshwar Kisan,
Subramani Lakshumanan,
Subbaiah Murugaiah A. M.,
Gupta Anuradha,
Bajpai Lakshmikant,
Bagadi Muralidhararao,
Mathur Arvind
Publication year - 2021
Publication title -
separation science plus
Language(s) - English
Resource type - Journals
ISSN - 2573-1815
DOI - 10.1002/sscp.202000046
Subject(s) - diastereomer , chemistry , acetonitrile , chromatography , conjugate , elution , valine , high performance liquid chromatography , organic chemistry , amino acid , biochemistry , mathematical analysis , mathematics
The production of pure diastereomers and the quality control of chiral drug substances have become key issues for the pharmaceutical industry and regulatory agencies due to differences in their biological properties in vivo. This study discusses the unusual case study for analytical method development and preparative purification of diastereomers derived from the conjugation of l ‐ and d ‐valine ester with the HIV‐1 protease inhibitor atazanavir prodrug. While the l ‐valine ester conjugate diastereomers could be successfully separated using acetonitrile and 10 mM ammonium acetate on SunFire‐C 18 OBD column, the corresponding d ‐valine ester conjugate diastereomers co‐eluted under the same method conditions. This observation led to a series of method development and optimization work that resulted in an improved chromatographic condition, using acetonitrile:2‐propanol (70:30) v/v combination as an organic modifier with 0.1% HCOOH on SunFire‐C18 column. The same method was further scaled up for isolation of individual diastereomers on preparative high‐performance liquid chromatography.