Quality control of cytostatic drug preparations—comparison of workflow and performance of Raman/UV and high-performance liquid chromatography coupled with diode array detection (HPLC-DAD)

Qualification and impact of a video-assisted control system in a chemotherapy compounding unit

“…Gravimetric control, if simple to implement without requiring expensive equipment, does not allow identification of the product 12 14. Among analytical methods used for preparations control, we can cite high-performance liquid chromatography (HPLC) with or without column (FIA: flow injection analysis) coupled with ultraviolet (UV) detection,11 15 16 high-performance thin-layer chromatography (HPTLC),17 spectrophotometer UV/IR (Multispec, Microdom Company),18 19 spectrophotometer UV used with or without Raman (QCRx, Icônes Services Company),20 21 and spectrophotometer UV/visible (DrugLog, Pharmacolog Company). Raman spectroscopy is a promising method with the advantage of not requiring sample collection, unlike the other analytical methods mentioned, thus avoiding chemical risk for both staff and environment 22 23.…”

Online Coupling of Size Exclusion Chromatography to Capillary Enhanced Raman Spectroscopy for the Analysis of Proteins and Biopharmaceutical Drug Products

“…23,24,30 Besides, Raman spectroscopy (RS) is a powerful technique to investigate the secondary and tertiary structure of proteins, 25,26,28,29,31 but in pharmaceutical products its use for structural elucidation may be limited due to a low molar concentration of the active pharmaceutical ingredient (API) compared to the excipients. 32 In combination with size exclusion chromatography (SEC) proteins can be separated from matrix compounds, e.g., formulating excipients or protein aggregates, in an aqueous mobile phase, thus maintaining their native structure and preserving their pharmaceutical activity. 14 RS detection coupled online to SEC enables the acquisition of Raman spectra of the monomeric protein separated from aggregates or fragments.…”

“…During biopharmaceutical product development, regulatory authorities such as EMA request a detailed characterization of drug candidates. The characterization includes the assessment of the higher-order structure, the molecular weight or size of the protein, and an impurity analysis regarding the formation of aggregates or fragments. , The last gained importance as recent studies indicate structural changes of aggregated protein species compared to the monomeric protein. − Size exclusion chromatography is suggested as an analytical technique for the investigation of molecular weight or size of the protein and the determination of protein aggregation and fragmentation. ,, Besides, Raman spectroscopy (RS) is a powerful technique to investigate the secondary and tertiary structure of proteins, ,,,, but in pharmaceutical products its use for structural elucidation may be limited due to a low molar concentration of the active pharmaceutical ingredient (API) compared to the excipients . In combination with size exclusion chromatography (SEC) proteins can be separated from matrix compounds, e.g., formulating excipients or protein aggregates, in an aqueous mobile phase, thus maintaining their native structure and preserving their pharmaceutical activity .…”