Development studies on determination of preservatives decomposition products

Preservatives are chemical substances whose role is to protect medicinal products against harmful changes caused by microorganisms. They are added to sterile medicinal products, such as eye drops and multidose solutions for injections, as well as to non-sterile products, such as water oral solutions, creams, gels, suppositories and capsules with liquid content. The most commonly used preservatives include: benzyl alcohol, butyl, ethyl, methyl and propyl p-hydroxybenzoates and their sodium salts. In medicinal products benzyl alcohol slowly oxidizes to benzaldehyde and benzoic acid while esters of p-hydroxybenzoic acid hydrolyze to p-hydroxybenzoic acid. HPLC methods were elaborated for identification and quantitative determination of the parabens, benzyl alcohol, active substances as well as their impurities in pharmaceuticals: oral solutions Amertil and Efforil (contain cetirizine hydrochloride or etilefrine hydrochloride and parabens), eye drops Difadol (contains diclofenac sodium and benzyl alcohol) and cream Tenasil (contains terbinafine hydrochloride and benzyl alcohol). The HPLC systems consisted of columns: Supelcosil LC-DP, Inertsil ODS-3 or Discovery HS F5 and three mobile phases mixtures of acetonitrile with buffers of various pH (3, 5 and 7) in proportions 45 : 55 (v/v). These systems have been characterized with appropriate selectivity (all the Rs values > 2) and sensitivity (LOD approx. 0.01 microg/mL). They also demonstrated satisfactory precision and a linear dependence between the analyte content and the peak area.