Determination of Extractable and Leachable Phthalates from Pharmaceutical Packaging by LC-MS/MS

A simple, rapid and sensitive method was developed for analyzing contamination of phthalates in pharmaceutical formulations viz parenteral, lotions and ophthalmic preparation as an extractable and leachable. These phthalates are esters of phthalic acid such as dimethyl phthalate (DMP), diethyl phthalate (DEP) and dibutyl phthalate (DBP) used as plasticizers in pharmaceutical plastic packaging which were quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chromatographic separation was achieved on a C18 column (100 mm x 4.6 mm, 5 & mu;m) and 5 mM ammonium acetate: acetonitrile (10:90, v/v) solvents used as a mobile phase having 0.5 mL/min flow rate with a total run time 4.5 min. The linearity range for DMP, DEP and DBP was set to 1-100 ng/mL. For all the analytes the mean of the coefficient of determination (r(2), n=3) were found to > 0.994, the precision values (%RSD) and overall % recovery were found to be acceptable. The significant amount of DMP, DEP, and DBP were found as extractable and leachable from the pharmaceutical products. On the basis of results, it was concluded that the proposed LC-MS/MS method was simple, reliable and robust. This method was used for determination of phthalates which are leached in pharmaceutical preparations liable to toxic potential in risk assessment.