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Surface‐activated chemical ionization‐electrospray ionization mass spectrometry combined with two‐dimensional serial chromatography is a powerful tool for drug stability studies
Author(s) -
Conti Matteo,
Motta Roberto,
Puggioli Cristina,
Brambilla Paolo
Publication year - 2013
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.6567
Subject(s) - chemistry , chromatography , electrospray ionization , mass spectrometry , analyte , liquid chromatography–mass spectrometry , selected reaction monitoring , analytical chemistry (journal) , ion suppression in liquid chromatography–mass spectrometry , tandem mass spectrometry
RATIONALE Drug stability is an important quality‐control issue for pharmaceutical and clinical practices. Among the analytical techniques that address this issue, liquid chromatography/mass spectrometry (LC/MS) can be very useful, especially when assessing the quality of liquid formulations, because it is intrinsically sensitive, selective, and a rapid analytical technique. However, LC/MS suffers from technical drawbacks, e.g., matrix effects, and the production of in‐source degradation products, which can limit its usefulness. METHODS To overcome the aforementioned drawbacks associated with LC/MS, we introduce an innovative approach (2D‐LC/SACI‐ESI‐MS/MS) that incorporates two‐dimensional liquid chromatography (2D‐LC) in conjunction with an MS system consisting of a surface‐activated chemical ionization‐electrospray ionization chamber ( SACI‐ESI), an ion trap MS analyzer, and tandem mass spectrometry. RESULTS To validate our 2D‐LC/SACI‐ESI‐MS/MS system stability studies were performed on the computerized tomography contrast agents, iohexol, iodixanol, iopamidol, iomeprol, iopromide, and iobitridol, either alone or in binary combination. The matrix effects, in‐source analyte degradation, and analytical performance were compared with those obtained using a one‐dimensional LC/MS configuration. The accuracy coefficient of variance (CV) = 1–4%, and degradation (loss of water and other chemical moieties) was greatly reduced, attesting to the usefulness of this system for drug stability measurements. CONCLUSIONS Our new approach improves the performance (sensitivity, accuracy, and signal stability) of LC/MS instrumentation for drug stability measurements by reducing signal suppression effects and in‐source chemical reactions. Copyright © 2013 John Wiley & Sons, Ltd.