Quantitative Measurement of Cyclosporin A in Blood by Time-of-Flight Mass Spectrometry

Abstract

Analytical methods have been developed for the detection and quantification of cyclosporin A (CsA) in blood using time-of-flight secondary-ion mass spectrometry (TOF-SIMS) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF-MS). Linear calibration curves were obtained for both methods in the range 25-2000 ng/mL in whole blood. The limit of detection (LOD) and limit of quantification (LOQ) were determined to be 7 and 23 ng/mL, respectively, for the TOF-SIMS method; the LOD and LOQ were 10 and 33 ng/mL, respectively, for the MALDI/TOF-MS method. Coefficients of variation ranged from 3 to 5% for the TOF-SIMS method and from 4 to 8% for the MALDI/TOF-MS method. Blood samples were also analyzed by a nonspecific method, fluorescence polarization immunoassay (FPIA), and by a specific method, high-performance liquid chromatography (HPLC). The TOF-MS results are in good agreement with the HPLC results, but not with the FPIA results. The TOF-MS methods can also provide information about CsA metabolites.

Applications of mass spectrometry in combinatorial chemistry

“…Immunoassays, however, generally have low reproducibility and reliability, and provide little to no selectivity between a drug and its metabolites. 18,19 This lack of specificity is a significant limitation because metabolites, although structurally similar to the parent compound, often have different biological activity. 20,21 Mass spectrometric analysis, on the other hand, allows for co-extracted metabolites to be identified and quantitatively monitored (unless they have the same molecular weight).…”

Quantitation of synthetic polymers using an internal standard by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

“…In addition, a fourth "S" advantage for MALDI-TOF MS should include spaciousness: the ability to analyze molecules across an extensive mass range. Although research has been focused on qualitative characterization of those macromolecules, the technique has gradually been applied to quantitative measurement: for biomolecules by Nelson and McLean [13] and Hercules et al [14] in 1994 and for synthetic polymeric compounds by Gardella et al [15] in 2002.…”

Quantitative analysis of technical polymer mixtures by matrix assisted laser desorption/ionization time of flight mass spectrometry

“…The principal activity in this area has been reported by Nelson et al [1] as well as by Hercules et al [2][3][4][5][6]. In their studies, proteins and peptides were analyzed and the intensities of single peaks were considered.…”

“…In the first report of a quantitative measurement utilizing MALDI by Hercules and co-workers [2], this group studied cyclosporin A in blood by TOF-SIMS and MALDI-TOF. Cyclosporin A belongs to a group of nonpolar, cyclic oligopeptides that have immunosuppressant activity.…”