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  • Identification of a mixed microparticle by combined microspectroscopic techniques: a real forensic case study in the biopharmaceutical industry.

Identification of a mixed microparticle by combined microspectroscopic techniques: a real forensic case study in the biopharmaceutical industry.

Applied spectroscopy (2010-08-20)
Xiaolin Cao, Peter Masatani, Gianpiero Torraca, Zai-Qing Wen
ABSTRACT

Identification of foreign microparticles in drug products is one of the first steps in evaluating the nature of particle contamination and its consequences for product quality. To characterize various foreign particles, we use spectral database search methods as well as a number of microscopic and microspectroscopic techniques. Here, we report a case study involving the identification and root-cause investigation of a microparticle consisting of four compounds. Foreign microparticles consisting of mixtures pose unique challenges for identification as their spectra are difficult to interpret and general database searches usually return unsatisfactory results. Moreover, sample separation through purification and other manipulations is time consuming and often difficult for these microparticles due to their small sizes and the limited quantities of the components. Here we demonstrate an applicable methodology that combines multiple microscopic and microspectroscopic techniques to identify a heterogeneous microparticle without the need for sample purification or chemical separation. This methodology primarily combines Raman, infrared, and energy dispersive X-ray microspectroscopic techniques to obtain complementary spectral information for the identification of heterogeneous particles. With this methodology, the mixed microparticle investigated in this study was determined to consist of polyisobutylene, hydrated magnesium silicate, titanium dioxide, and silica, likely originating from the vial stopper material.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Polyisobutylene, average Mw ~500,000, average Mn ~200,000 by GPC/MALLS, average Mv ~420,000
Sigma-Aldrich
Polyisobutylene, average Mw ~1,000,000, average Mn ~600,000 by GPC/MALLS, average Mv ~1,200,000
Supelco
Florisil® Adsorbent for Chromatography, 60-100 mesh
Supelco
Florisil® Adsorbent for Chromatography, 30-60 mesh
Supelco
Florisil®, <200 mesh, fine powder
Supelco
Florisil®, for the determination of hydrocarbon acc. to ISO 9377-2
Supelco
Florisil®, PR grade, 60-100 mesh, coarse powder
Supelco
Florisil®, 100-200 mesh, fine powder
Supelco
Florisil® PR, PR grade (analysis acc. to FDA)
Sigma-Aldrich
Florisil®, 100-200 mesh