Compatibility study of a parenteral microdose polyethylene glycol formulation in medical devices and identification of degradation impurity by 2D-LC/MS

Current developments in LC-MS for pharmaceutical analysis

“…In heart-cutting mode, the effluent of a first-dimension separation is only collected in a region of particular interest (e.g., where compounds are co-eluting) and re-injected on a seconddimension column for further separation. Typical applications of heart-cutting 2D-LC in pharmaceutical analysis involve the isolation of impurities from the active pharmaceutical ingredient (API) or an interfering matrix in the first dimension, the combination of achiral and chiral columns for the separation of enantiomers in the second dimension, and online desalting of peaks eluting in MSincompatible mobile phases in the first dimension 83,[85][86][87] .…”

“…Online heart-cutting 2D-LC was for example applied to identify an unknown impurity that was formed when an API was stored in an IV delivery device in the presence of polyethylene glycol (PEG) 85 . This impurity co-eluted with PEG, but could clearly be detected in UV due to the lack of UV-absorbance of PEG.…”

Recent Advances in Chromatography for Pharmaceutical Analysis

“…This approach has been widely applied for resolving closely related compounds (i.e., structurally related impurities, isomers or degradation products) in pharmaceutical analyses, 30 especially those performed through the coupling of orthogonal RP selectivities or those involving achiral-chiral analysis. 31 Page 10 of 74 ACS Paragon Plus Environment Analytical Chemistry 32 Dai et al 33 applied heart-cutting 2D RPLC-RPLC to perform comparison studies of parenteral microdoses of polyethylene glycol formulations in medical devices. Due to the increased selectivity and sensitivity provided by the second dimension, trace impurities were identified and then structurally characterized by MS.…”

“…In another contribution, Iguiniz et al demonstrated the power of 2D LC− SFC separations that included an achiral RPLC column in the first dimension and chiral SFC conditions in the second dimension. 32 Dai et al 33 applied heart-cutting 2D RPLC− RPLC to perform comparison studies of parenteral microdoses of polyethylene glycol formulations in medical devices. Due to the increased selectivity and sensitivity provided by the second dimension, trace impurities were identified and then structurally characterized by MS.…”