Analytical method for the determination and a survey of parabens and their derivatives in pharmaceuticals.

Exposure of humans to parabens is a concern due to the estrogenic activity of these compounds. Parabens are widely used as preservatives in some personal care products, foodstuffs and pharmaceuticals owing to their low cost, high water solubility and broad spectrum antimicrobial properties. Despite this, little is known on the occurrence of parabens in pharmaceutical products. In this study, a method based on solid-liquid or liquid-liquid extraction (SLE or LLE), and high performance liquid chromatography (HPLC) coupled with triple quadrupole tandem mass spectrometry (QqQ or MS/MS) was developed for the determination of six most frequently used parabens and four paraben derivatives (methyl- and ethyl-protocatechuates, and mono- and di-hydroxybenzoic acids) in pharmaceuticals. A sample-purification step involving solid phase extraction (SPE) was optimized for the analysis of solid and lipid-rich pharmaceuticals. To our knowledge, this is the first comprehensive report on the occurrence of parabens in pharmaceuticals. The developed method was applied for the analysis of 128 liquid/syrup, cream, solid, prescription or over-the counter (OTC) drugs collected from the USA and a few other countries in Europe and Asia. Although majority of the drugs analyzed in the study did not contain parabens, concentrations as high as 2 mg/g were found in some drugs. Methyl- and propyl- parabens were the frequently detected compounds. 4-Hydroxybenzoic acid was the major metabolite found in pharmaceutical products.