期刊
JOURNAL OF CHROMATOGRAPHY A
卷 1259, 期 -, 页码 100-110出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.chroma.2012.01.009
关键词
Impurity profiling; Amino acids; Peptides; Off-line two dimensional liquid chromatography; Charged aerosol detector; Unified calibration function
资金
- Austrian Christian Doppler Research Society
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) x 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. (c) 2012 Elsevier B.V. All rights reserved.
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