Separation of the stereoisomers of an allenic E-type prostaglandin.
Enprostil (I) is a synthetic dehydro-prostaglandin E2 containing a chiral allene moiety which is unresolved relative to the four remaining chiral centers. The relative configuration of the four remaining chiral centers is consistent with that of the naturally occurring E series of prostaglandins. Thus, enprostil exists as enantiomeric pairs of two allenic epimers. An analytical procedure has been developed that separates the four optical isomers present in enprostil. This procedure involves, first, the acid-catalyzed dehydration of enprostil to its corresponding prostaglandin A analogue followed by derivatization with beta-naphthylsulfonyl-L-prolyl chloride. The resulting diastereomeric sulfonate esters are separated on an achiral silica gel high-performance liquid chromatographic column. This procedure has been applied to the analysis of both enprostil drug substance and enprostil formulated in a propylene carbonate solution from soft elastic gelatin capsules. An efficient procedure for the recovery of enprostil from the solution formulation is also described.
Kern
J R
JR
Analytical and Environmental Research, Syntex Research, Syntex USA Inc., Palo Alto, CA 94304.
Lokensgard
D M
DM
Manes
L V
LV
Matsuo
M
M
Nakamura
K
K
D002851:Chromatography, High Pressure Liquid; D011459:Prostaglandins E, Synthetic / Q000302:isolation & purification*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D011459:Prostaglandins E, Synthetic