Reduction of Internal Standard Signals in Quantitative MALDI-TOF Mass Spectrometry — Oak Academic Publishing
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Reduction of Internal Standard Signals in Quantitative MALDI-TOF Mass Spectrometry
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA
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Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, Greensboro, USA.
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Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, Greensboro, USA.
1 Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA
2 Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, Greensboro, USA.
3 Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, Greensboro, USA.
The advantages of combining qualitative and quantitative analysis on a single analytical technique have further extended the applications of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to the quantitation of various biomolecules. To achieve absolute quantitation, it is necessary to perform a calibration with standard dilutions. For the purpose of measuring DNA samples, a pure DNA oligonucleotide at different concentrations was chosen as a standard to perform the calibration of MALDI-TOF MS. In order to overcome the variation of signal intensity from repeated measurements of each DNA standard dilution, fixed amount of an internal standard was added into each DNA standard dilution. Instead of maintaining at a constant level, the signals of fixed amount of internal standard were decreased 73% from its initial level while the signals of DNA standard continued to increase within a linear dynamic range for quantitation from 0.20 μM to 12.5 μM of DNA. Attempts to identify the cause of signal reduction were systematically carried out. This is the first report on the extent of signal reduction in quantitative MALDI-TOF MS. These results represent a limitation on using MALDI-TOF MS to monitor the changes in concentration of two different compounds within a chemical or biological system.
KeywordsMALDIMass SpectrometryQuantitation
D. Feny? and R. C. Beavis, “Informatics Development: Challenges and Solutions for MALDI Mass Spectrometry,” Mass Spectrometry Reviews, Vol. 27, No. 1, 2008, pp. 1-19. doi:10.1002/mas.20152
J. Ragoussis, G. P. Elvidge, K. Kaur and S. Colella, “Matrix-Assisted Laser Desorption/Ionisation, Time-of-Flight Mass Spectrometry in Genomics Research,” PLoS Genetics, Vol. 2, 2006, p. e100. doi:10.1371/journal.pgen.0020100
S. Douthwaite and F. Kirpekar, “Identifying Modifications in RNA by MALDI Mass Spectrometry,” Methods in Enzymology, Vol. 425, 2007, pp. 1-20. doi:10.1016/S0076-6879(07)25001-3
J. Schiller, R. Suss, B. Fuchs, M. Muller, O. Zschornig and K. Arnold, “,” Frontiers in Bioscience, Vol. 12, 2007, pp. 2568-2579. doi:10.2741/2255
M. L. Reyzer and R. M. Caprioli, “MALDI-MS-Based Imaging of Small Molecules and Proteins in Tissues,” Current Opinion in Chemical Biology, Vol. 11, No. 1, 2007, pp. 29-35. doi:10.1016/j.cbpa.2006.11.035
D. J. Harvey, “Structural Determination of N-Linked Glycans by Matrix-Assisted Laser Desorption/Ionization and Electrospray Ionization Mass Spectrometry,” Proteomics, Vol. 5, No. 7, 2005, pp. 1774-1786. doi:10.1002/pmic.200401248
G. Bolbach, “Matrix-Assisted Laser Desorption/Ionization Analysis of Non-Covalent Complexes: Fundamentals and Applications,” Current Pharmaceutical Design, Vol. 11, No. 20, 2005, pp. 2535-2557. doi:10.2174/1381612054546923
T. Satoh, T. Sato and J. Tamura, “Development of a High-Performance MALDI-TOF Mass Spectrometer Utilizing a Spiral Ion Trajectory,” Journal of the American Society for Mass Spectrometry, Vol. 18, No. 7, 2007, pp. 1318-1323. doi:10.1016/j.jasms.2007.04.010
A. Chacon, I. Zagol-Ikapitte, V. Amarnath, M. L. Reyzer, J. A. Oates, R. M. Caprioli and O. Boutaud, “On-Tissue Chemical Derivatization of 3-Methoxysalicylamine for MALDI-Imaging Mass Spectrometry,” Journal of Mass Spectrometry, Vol. 46, No. 8, 2011, pp. 840-846. doi:10.1002/jms.1958
C. A. Barnes and N. H. L. Chiu, “Accurate Characterization of Carcinogenic DNA Adducts Using MALDI Tandem Time-of-Flight Mass Spectrometry,” International Journal of Mass Spectrometry, Vol. 279, No. 2-3, 2009, pp. 170-175. doi:10.1016/j.ijms.2008.10.006
W. Yang and N. Chiu, “Comparison of Accuracy on DNA Quantitation Determined by MALDI-TOF Mass Spectrometry and UV Spectrometry,” Spectroscopy Letters, Vol. 43, No. 7-8, 2010, pp. 602-608. doi:10.1080/00387010.2010.510766
R. W. Garden and J. V. Sweedler, “Heterogeneity within MALDI Samples as Revealed by Mass Spectrometric Imaging,” Analytical Chemistry, Vol. 72, No. 1, 2000, pp. 30-36. doi:10.1021/ac9908997
L. K. Zhang and M. L. Gross, “Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Methods for Oligodeoxynucleotides: Improvements in Matrix, Detection Limits, Quantification, and Sequencing,” Journal of The American Society for Mass Spectrometry, Vol. 11, No. 10, 2000, pp. 854-865. doi:10.1016/S1044-0305(00)00161-6
W. T. Berggren, T. Takova, M. C. Olson, P. S. Eis, R. W. Kwiatkowski and L. M. Smith, “Multiplexed Gene Expression Analysis Using the Invader RNA Assay with MALDI-TOF Mass Spectrometry Detection,” Analytical Chemistry, Vol. 74, No. 8, 2002, pp. 1745-1750. doi:10.1021/ac011167t
K. Tang, S. L. Allman, R. B. Jones and C. H. Chen, “Quantitative Analysis of Biopolymers by Matrix-Assisted Laser Desorption,” Analytical Chemistry, Vol. 65, No. 15, 1993, pp. 2164-2166. doi:10.1021/ac00063a041
D. Sarracino and C. Richert, “Quantitative MALDI-TOF MS of Oligonucleotides and a Nuclease Assay,” Bioorganic & Medicinal Chemistry Letters, Vol. 6, No. 21, 1996, p. 3057. doi:10.1016/0960-894X(96)00465-9
B. A. Bruenner, T.-T. Yip and T. W. Hutchens, “Quantitative Analysis of Oligonucleotides by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, Vol. 10, No. 14, 1996, pp. 1797-1801. doi:10.1002/(SICI)1097-0231(199611)10:14 3.0.CO;2-5
K. Tang, S. L. Allman and C. H. Chen, “Matrix-Assisted Laser Desorption Ionization of Oligonucleotides with Various Matrices,” Rapid Communications in Mass Spectrometry, Vol. 7, No. 10, 1993, pp. 943-948. doi:10.1002/rcm.1290071016
J. M. Koomen, W. K. Russell, J. M. Hettick and D. H. Russell, “Improvement of Resolution, Mass Accuracy, and Reproducibility in Reflected Mode DE-MALDI-TOF Analysis of DNA Using Fast Evaporation-Overlayer Sample Preparations,” Analytical Chemistry, Vol. 72, No. 16, 2000, pp. 3860-3866. doi:10.1021/ac0001941
A. Honda, H. Sonobe, A. Ogata and K. Suzuki, “Improved Method of the MALDI-TOF Analysis of DNA with Nanodot Sample Target Plate,” Chemical Communications, Vol. 42, 2005, pp. 5340-5342. doi:10.1039/b507065a
L. J. Dekker, J. C. Dalebout, I. Siccama, G. Jenster, P. A. Sillevis Smitt and T. M. Luider, “A New Method to Analyze Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Peptide Profiling Mass Spectra,” Rapid Communications in Mass Spectrometry, Vol. 19, No. 7, 2005, pp. 865-870. doi:10.1002/rcm.1864
A. I. Gusev, W. R. Wilkinson, A. Proctor and D. M. Hercules, “Direct Quantitative Analysis of Peptides Using Matrix Assisted Laser Desorption Ionization,” Fresenius’ Journal of Analytical Chemistry, Vol. 354, No. 4, 1996, pp. 455-463. doi:10.1007/s0021663540455
B. A. Garcia, P. J. Heaney and K. Tang, “Improvement of the MALDI-TOF Analysis of DNA with Thin-Layer Matrix Preparation,” Analytical Chemistry, Vol. 74, No. 9, 2002, pp. 2083-2091. doi:10.1021/ac011089+
H. Chen and M. He, “Quantitation of Synthetic Polymers Using an Internal Standard by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry,” Journal of The American Society for Mass Spectrometry, Vol. 16, No. 1, 2005, pp. 100-106. doi:10.1016/j.jasms.2004.09.024
R. Knochenmuss, “Photoionization Pathways and Free Electrons in UV-MALDI,” Analytical Chemistry, Vol. 76, No 11, 2004, pp. 3179-3184. doi:10.1021/ac035501s
Y. Kong, Y. Zhu and J. Y. Zhang, “Ionization Mechanism of Oligonucleotides in Matrix-Assisted Laser Desorption/ Ionization Time-of-Flight Mass Spectrometry,” Rapid Communications in Mass Spectrometry, Vol. 15, No. 1, 2001, pp. 57-64. doi:10.1002/1097-0231(20010115)15:1 3.0.CO;2-7
R. Knochenmuss, “A Quantitative Model of Ultraviolet Matrix-Assisted Laser Desorption/Ionization Including Analyte Ion Generation,” Analytical Chemistry, Vol. 75, No. 10, 2003, pp. 2199-2207. doi:10.1021/ac034032r
G. Westmacott, W. Ens, F. Hillenkamp, K. Dreisewerd and M. Schurenberg, “The Influence of Laser Fluence on Ion Yield in Matrix-Assisted Laser Desorption Ionization Mass Spectrometry,” International Journal of Mass Spectrometry, Vol. 221, No. 1, 2002, pp. 67-81. doi:10.1016/S1387-3806(02)00898-9