Category: Formulation and Quality
Purpose: The use of Captisol® (Betadex Sulfobutyl Ether Sodium) as a solubilizing or stabilizing agent with injectable drug products is being investigated. The detection of Silicon (Si) in Captisol is necessary since Si species can compete for the hydrophobic cyclodextrin cavity. Si is used widely in the pharmaceutical industry as a coating for tubing, stoppers and syringes. A novel approach to this detection is utilizing heated acid digestion and analysis by ICP-MS. Until now a solvent based extraction with Toluene was being used to look for Silicon Hydroxide using Polydimethylsiloxane (PDMS) as a reference standard. Validating a heated acid digestion would allow the use of single element standard Silicon within an aqueous based extraction.
Methods: Heated hot block with digestion cups ICP-MS with Platinum Injector and PFA Spray Chamber
Results: After investigation of different consumables for the ICP-MS (platinum injector, PFA spray chamber and nebulizer) a reasonable LOD and LOQ was established along with a reproducible calibration curve with R > 0.9999 with concentration values of 0.1, 5, and 10 ppm. After Captisol blank subtraction near 100% recovery of known spiked samples with Silicon standard at 0.5, 4, and 8 ppm. Method validation passed all criteria of accuracy, repeatability, linearity, and range that was set forth.
Conclusion: The analysis for silicon was successfully completed such that should silicon be present in Captisol final drug products it would be detected by ICP-MS utilizing an aqueous acid digestion.