Quantitative gas and thin-layer chromatographic determination of methylparaben in pharmaceutical dosage forms.

Methyl p-hydroxybenzoate (methylparaben) is one of the most important pharmaceutical preservatives. The determination of methylparaben in multi-component pharmaceutical preparations is complicated by the fact that its total concentration seldom exceed 0.1% of the formulation. The possibility that it can interact chemically with active ingredients’ led to a need for a rapid and reliable quantitative method for the determination of methylparaben in dosage forms. Some methods for the quantitative and semiquantitative determination of parabens have been published*-‘, but less attention has been paid to the pre-treatment of dosage forms. Quantitation of preservatives in pharmaceutical preparations poses a considerable analytical problem. Owing to the complex matrix present and the high concentrations of excipients, even chromatographic quantitation cannot be carried out without an extensive preliminary cleanup. Previously reported multiple extraction methods are time consuming and often give poor recoveries. In the work described here a single extraction step precedes the quantitation. Extrelut (Merck) columns were used. The aqueous mixtures of the preparations were added to the column and the methylparaben was eluted with diethyl ether or ethanol, depending on the composition of the formulation. The interfering excipients can be eliminated by this simple procedure and at the same time the recovery of methylparaben is very good. The paraben content of the eluate can be determined quantitatively by either gas (GC) or thin-layer chromatography (TLC). To demonstrate the feasibility of the methods for the determination of methylparaben in dosage forms, the procedures were applied to the analysis of some mucilages, syrups and ointments listed in the Hungarian Pharmacopoeia.