Liquid chromatographic separation of zalcitabine and its stereoisomers.
A liquid chromatographic method capable of separating and quantitating the stereoisomers of zalcitabine has been developed and validated. The separation was achieved with an Astec Cyclobond I--RSP column and a mobile phase of 0.25% triethylamine in water adjusted to a pH of 6.5 with glacial acetic acid. All enantiomers were found to exhibit a linear response in the range of 0.1-10% in the presence of 100% zalcitabine. Precision of analysis was found to be less than 1.5% at a level of 1% relative to zalcitabine. The limit of detection for two of the three enantiomeric impurities was determined to be 0.05% relative to zalcitabine. The detection limit for the third was found to be 0.1%. This method was successfully applied to the analysis of reference standards and several production scale batches. All of these materials were found to be stereochemically pure to a level of 99.8% or better.
Scypinski
S
S
Hoffmann-La Roche, Inc., Nutley, NJ 07110-1199.
Ross
A J
AJ
D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins; D006863:Hydrogen-Ion Concentration; D012997:Solvents; D013237:Stereoisomerism; D016047:Zalcitabine / Q000302:isolation & purification*
D003505:Cyclodextrins; D012997:Solvents; D016047:Zalcitabine