ABSTRACT
A normal-phase high-performance liquid chromatographic method was used for the determination of methyl carboprost and acid-catalyzed degradation products in a polymer-based, controlled release dosage form. A reversed-phase method was used to isolate sufficient quantities of the degradation products to determine their identity. Degradation of methyl carboprost under acidic conditions results in epimerization and dehydration, to several isomers, at the tertiary allylic hydroxyl group. Mass balance was 94% for a sample allowed to degrade 50%. These compounds were observed to form in the polymer-based, controlled release dosage form. For the determination of methyl carboprost in the dosage form, the method was found to be linear, precise with a relative standard deviation of 2% and to have an average recovery of 99.2%.
Subject(s)
Carboprost/analysis , Prostaglandins F, Synthetic/analysis , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid/methods , Drug Stability , Hydrogen-Ion Concentration , Membranes, Artificial , PolymersABSTRACT
A high-pressure liquid chromatographic assay for carboprost tromethamine as the bulk drug and in a sterile solution formulation is described. The procedure involves derivatization of the prostaglandin to form the UV-absorbing naphthacyl ester, which then is chromatographed on a silica gel column using methylene chloride-1,3-butanediol-water (496:4:0.25) as the mobile phase. This procedure is compared with a nonderivatization procedure with refractive index detection. Both procedures separate the 15R-epimer of carboprost from carboprost, but only the derivatization procedure separates the 5-trans-isomer of carboprost. Possible reasons for the better separation using the derivatization procedure are discussed. Both procedures gave a coefficient of variation of approximately 1% for carboprost. The derivatization procedure gave a coefficient of variation of approximately 7% for the 15R-epimer and 5-trans-isomer when present at 2% of the carboprost level.
