Separation and Characterization of Standard Propoxyphene Diastereomers and Their Determination in Pharmaceutical and Illicit Preparations

Abstract

Due to the existence of 2 asymmetric carbon atoms in the propoxyphene molecule, there are 4 diastereomers: alpha dextro, alpha levo, beta dextro, and beta levo. Only alpha-d-propoxyphene is included under the federal Controlled Substances Act. Baseline separations of propoxyphene from various incipients (aspirin, caffeine, phenacetin, and acetaminophen) present in pharmaceutical and illicit preparations, and between the alpha and beta diastereomers, were achieved by high pressure liquid chromatography. The column eluant was collected and propoxyphene was extracted. The optical isomers were differentiated and characterized by melting points and by chemical microcrystalline tests. Using hot stage thermomicroscopy, the eutectic melting points of binary isomeric mixtures of propoxyphene bases and salts were found to be depressed about 10 degrees and 15-30 degrees C, respectively, below the individual isomer melting points. The characteristic microcrystals formed with the alpha racemic mixtures by using a glycerin-aqueous gold chloride reagent were not produced by the beta racemic mixtures.