Study of the matrix effect on the PIXE quantification of active pharmaceutical ingredients in different formulations

Abstract

While Particle Induced X-ray Emission technique (PIXE) is an accurate technique to quantify Active Pharmaceutical Ingredients (API’s) via the analysis of their heteroatoms, each drug (formulation) may require a specific quantification procedure due to its distinct matrix composition.The commercial Fludinium® drug, which has two active ingredients Clidinium Bromide (C22H26NO3Br) and Dihydrochloride Trifluoperazine (C21H24N3F3S. 2HCl) has been taken as a case study in this work. Different amounts of its API’s and its placebo were mixed to provide various formulations.The matrix effect on the quantification of the three heteroatoms (chlorine, sulfur and bromine) related to the above API’s in different formulations has been studied. In fact, chlorine which is in its hydrochloride form in the API was not eventually considered for calculation due to its instability under beam. The calculation of bromine amount via its Kα or its Lα rays was found to be independent of the matrix composition and it was rapidly done by simple comparison to an external standard. However, the calculation of sulfur, via its Kα, was highly dependent on the matrix composition. Therefore, to achieve an accurate quantification a more sophisticated calculation method was used by means of the GUPIX code.