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Applications of hyphenated LC‐MS techniques in pharmaceutical analysis
Author(s) -
Ermer Joachim,
Vogel Martin
Publication year - 2000
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/1099-0801(200010)14:6<373::aid-bmc29>3.0.co;2-s
Subject(s) - chemistry , chromatography , mass spectrometry , quality by design , resolution (logic) , impurity , process development , pharmaceutical drug , enantiomer , chromatographic separation , drug , high performance liquid chromatography , process engineering , organic chemistry , computer science , pharmacology , medicine , artificial intelligence , particle size , engineering
In pharmaceutical analysis, ie the analytical development and quality control of drug substances and dosage forms, mass spectrometry (MS) combined with chromatographic separation is perhaps the most powerful technique for the monitoring, characterization and identification of impurities. The addition of further dimensions to chromatographic separations by hyphenated techniques offers unique possibilities of efficiently supporting pharmaceutical development and ensuring the quality and safety of pharmaceuticals. However, the ionization process in MS involves some characteristics which have to be recognized and taken into account for an appropriate application as well as the evaluation of the results. Chromatographic method development and validation can be supported very effectively by MS detection, eg in the investigation of coelution and peak purity. Chiral amino acid analysis is largely facilitated by the mass‐specific detection of the derivatized amino acid enantiomers, which ignores all other interfering substance peaks. Examples are presented for the use of LC‐MS‐MS fragmentation and high‐resolution MS in the structural elucidation of degradation products and impurities. LC‐MS is systematically applied to monitor impurity profiles during pharmaceutical development and scaling up and supports the safety evaluation of batches used in clinical studies. Copyright © 2000 John Wiley & Sons, Ltd. Abbreviations used: APCI atmospheric pressure chemical ionizationAPI atmospheric pressure ionizationCFFAB continuous flow‐fast atom bombardmentCI chemical ionizationEI electron impactESI electrospray ionizationFT‐ICR Fourier transform ion cyclotron resonancePB particle beamRI refractive indexTOF time‐of‐flightTSP thermospray.