title: Comprehensive impurity profiling of nutritional infusion solutions by multidimensional off-line reversed-phase liquid chromatography × hydrophilic interaction chromatography-ion trap mass-spectrometry and charged aerosol detection with universal calibration.
abstract: A new analysis strategy was employed for the establishment of a comprehensive qualitative and quantitative impurity profile of a stressed multi-constituent pharmaceutical drug formulation, namely a nutritional infusion solution composed of amino acids and dipeptides. To deal with the highly complex samples a multidimensional analysis approach was developed which made use of an off-line two-dimensional reversed-phase liquid chromatography (RPLC)×hydrophilic interaction chromatography (HILIC) separation and combination of complementary detection involving ion trap mass spectrometry (IT-MS) and a charged aerosol detector (CAD). The CAD is a mass-sensitive universal detector for non-volatile compounds with relatively consistent detector response. A universal calibration function was set up with a set of standards. This universal calibration function was then employed to quantify unknown impurities allowing their classification into those that need to be reported (>0.05% relative to the precursor compound), identified (>0.1%), and quantified (>0.15%). The dilemma of unavailability of authentic standards at this stage of research for quantification could thereby be circumvented. Relevant impurities above the reporting threshold were identified by IT-MS. Impurities detected comprised di-, tri- and tetrapeptides, cyclic dipeptides (diketopiperazines), pyroglutamic acid derivatives and their condensation products. Cross-validation with HPLC-MS/MS methods using synthesized authentic standards confirmed the results obtained by the presented multidimensional analysis assay.
authors.affiliation: University of Vienna, Christian Doppler Laboratory for Molecular Recognition Materials, Department of Analytical Chemistry, Waehringerstrasse 38, A-1090 Vienna, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Schiesel
authors.forename: Michael
authors.initials: M
authors.lastname: Lämmerhofer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lindner
mesh_terms: D000336:Aerosols / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase / Q000379:methods* / Q000592:standards; D004340:Drug Contamination; D057927:Hydrophobic and Hydrophilic Interactions; D013058:Mass Spectrometry / Q000379:methods*; D009842:Oligopeptides / Q000032:analysis; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D015203:Reproducibility of Results
chemical_list: D000336:Aerosols; D009842:Oligopeptides; D019999:Pharmaceutical Solutions