Analysis of Plasticizers in Finished Drug Products
Plasticizers can be directly as well as indirectly introduced into drugs. Some are for example used in films covering tablets, dragees and capsules as well as for packaging materials. In general packaging components should be constructed of materials that will not leach harmful or undesirable amounts of substances into the drug product. During extraction studies the suitability of primary and secondary packaging materials has to be determined by applying different solvents, pH and temperatures that exceed normal storage conditions. A combination of methods can be used for screening, quantifying and identifying extracted materials. When establishing an extraction profiles this requires means for identification. This is done by mass spectrometry with GC/MS or LC/MS.
 Typical substances that can be extracted from plastic material are phthalate esters. They are used as lubricants and can be determined using GC/MS with chemical ionization (CI). The figure shows PCI methane mass spectrum of di-n-butyl phthalate. It shows substantial fragmentation but relative to the EI spectrum high abundance for the higher m/z ions such as the protonated molecule at m/z 279. The ion at m/z 205 is generated by loss of an oxybutyl fragment
Applying GC - electron impact (EI) mass spectrometry to the determination of phthalates requires full chromatographic separation. The EI spectra of the phthalates are distinguished only by ions of very low intensity. In EI, the phthalates produce a single common ion (m/z 149) as the most intense spectral peak, regardless of the alkyl side chain substitution. Applying tandem mass spectrometry (i.e., EI/MS/MS) gains nothing, because there is a common parent ion, and therefore any daughter ions would also be non-unique. However, the combination of positive chemical ionization with retention-time locking allows even complex mixtures of phthalates to be characterized. Ammonia reagent gas produces the protonated molecule as the base peak, which immediately allows the phthalates to be distinguished on the basis of their substitution. PCI is also an advantage in complex matrices, where the non selective ionization of EI produces a high chemical background. This method should therefore be suitable for use in phthalate determinations in plastics.
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