High-performance liquid chromatographic analysis of codeine in syrups using ion-pair formation

The chromatographic behavior of morphine, codeine, and ethylmorphine was examined using reversed-phase high-performance liquid chromatography and ion-pair formation. Alkyl sulfonates and sulfates significantly increased the retention times for these compounds. The carbon chain length of the pairing ions was linearly related to the log of the capacity factors of these amine drugs. A mechanism for the increased retention based on ion-pair formation in the mobile phase is proposed. The use of dioctyl sodium sulfosuccinate as a pairing ion for codeine is described, and a method utilizing this pairing ion was developed for the quantitation of codeine in syrups. This method was applied successfully to various syrups containing codeine or codeine phosphate.