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Simultaneous quantification of cyclosporin A and its major metabolites by time‐of‐flight secondary‐ion mass spectrometry and matrix‐assisted laser desorption/ionization mass spectrometry utilizing data analysis techniques: Comparison with high‐performance liquid chromatography
Author(s) -
Muddiman David C.,
Gusev Arkady I.,
Proctor Andrew,
Hercules David M.,
Tata Prasad,
Venkataramanan Raman,
Diven Warren
Publication year - 1995
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1190301013
Subject(s) - chemistry , mass spectrometry , chromatography , analytical chemistry (journal) , time of flight mass spectrometry , ionization , time of flight , matrix assisted laser desorption/ionization , metabolite , high performance liquid chromatography , surface enhanced laser desorption/ionization , ion , desorption , sample preparation in mass spectrometry , electrospray ionization , biochemistry , organic chemistry , adsorption
Simultaneous quantification of cyclosporin A (CsA) and its major metabolite (AM1) in blood has been achieved using time‐of‐flight secondary‐ion mass spectrometry (TOF‐SIMS) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI/TOF‐MS). Previous investigations indicated that spectral interferences exist in the analysis of CsA blood samples by the above methods. In TOF‐SIMS, interference is caused by overlap of the Ag‐cationized internal standard, cyclosporin D (CsD), with the Ag‐cationized metabolite, AM1. To resolve this interference and obtain quantitative information, cross‐correlation analysis was applied to the TOF‐SIMS data. Application of damped non‐linear least squares curve‐fitting was carried out to resolve an interference in the MALDI/TOF‐MS data due to multiple cationization products (i.e. Na and K). Measurement of standard samples indicates that the minimum accuracy (95% confidence level) of the TOF‐SIMS method was better than 9% for CsA and 13% for AM1 using only one standard curve'. Similarly, the minimum accuracy of the MALDI/TOF‐MS method was determined to be 14% for CsA and better than 25% for AM1. Blood samples obtained from transplant patients receiving CsA were analyzed by polyclonal fluorescence polarization immunoassay, high‐performance liquid chromatography (HPLC), and by both TOF‐MS methods. Both TOF‐MS results for CsA and mono‐hydroxylated CsA are in good agreement with the HPLC results.