Stereochemical impurities

There are also known cases of drug enantiomers that possess completely different therapeutic properties. The (+)-2/ ,35 -stereoisomer of propoxyphene (dextropropoxyphene) is marketed as an analgesic agent, whereas its enantiomer ( )-(25, 3/ )-propoxyphene (levopropoxyphene) is available as an effective anti-tussive agent [3]. The enantiomers of some chiral drugs are known to possess essentially identical qualitative and quantitative pharmacological activities, for example, the antihistamine promethazine, which is marketed as a racemate [5]. 

Stereochemical impurities present in drug substances or drug products can arise from a number of different sources. Armstrong et al. performed an extensive study in the 1990s focusing on enantiomeric impurities in chiral synthons 

Although the majority of current pharmacopoeial methods describe the use of specific optical rotation ([a]) for the determination of stereoisomer identity and/or content, separation techniques such as HPLC and CE are now the most frequently applied technologies during drug development and for new pharmaceutical products entering the market. Indeed, Supplementary Chapter K in Volume IV of the 2004 British Pharmacopoeia (BP) deals with this specific issue [22]. It states that in future when a monograph describes an enantiomer it will include both a test for identity ([a]) and a test to control stereoisomeric purity 

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The potential contamination from either stereochemical impurities or stereochemical inversion of NSAID S (such as etodolac) that might take place when using ethyl chloroformate as the derivatizing agent in the sample preparation described above [33] was investigated in a separate study [34]. The study concluded that the extent of stereochemical conversion induced by assay procedures was small (approximately 1%) for... 

Scheme 3. Chain-End Epimerization as a Source of Stereochemical Impurities...

This polymer in its commercial form exhibits sufficient photoconductivity to be used in imaging processes in spite of its stereochemical impurity and conformational disorder. Simple uniaxial creep experiments on thin films above the glass transition temperature were shown to produce only small orientations, i.e. order parameters < 2) when defined in the... 

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