کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1202323 | 1493666 | 2012 | 11 صفحه PDF | دانلود رایگان |
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.
► Comprehensive analysis of complex drug formulation.
► Orthogonal separation methods and complementary detection.
► Universal detection by CAD for preliminary quantitation.
► HPLC hyphenated with ESI-ion-trap-MS for qualitative analysis.
► Rapid classification of impurities according to their relevance.
Journal: Journal of Chromatography A - Volume 1259, 12 October 2012, Pages 100–110