Experimental design for optimizing MALDI-TOF-MS analysis of palladium complexes

Tijana M. Rakić-Kostić, Jovana V. Bogojeski, Iva A. Popović, Maja D. Nešić, Boris M. Rajčić, Marija R. Nišavić, Marijana Ž. Petković, Suzana R. Veličković


This paper presents optimization of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer (MS) instrumental parameters for the analysis of chloro(2,2',2"-terpyridine)palladium(II) chloride dihydrate complex applying design of experiments methodology (DoE). This complex is of interest for potential use in the cancer therapy. DoE methodology was proved to succeed in optimization of many complex analyt­ical problems. However, it has been poorly used for MALDI-TOF-MS optimization up to now. The theoretical mathematical relationships which explain the influence of important experimental factors (laser energy, grid voltage and number of laser shots) on the selected responses (signal to noise – S/N ratio and the resolution – R of the leading peak) is est­ablished. The optimal instrumental settings providing maximal S/N and R are identified and experimentally verified.


MALDI-TOF-MS; design of experiments (DoE); optimization; metallo-drugs

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S.J. Wetzel, M.C.M. Guttman, K.M. Flynn, J.J. Filliben, Significant parameters in the optimization of MALDI-TOF-MS for synthetic polymers, J. Am. Soc. Mass Spectrom. 17 (2006) 246–252.

B. Dejaegher, Y.V. Heyden, Experimental designs and their recent advances in set-up, data interpretation and analytical applications, J. Pharm. Biomed. Anal. 56 (2011) 141–158.

N. Kostić, Y. Dotsikas, A. Malenović, B. Jancić Stojanović, T. Rakić, D. Ivanović, M. Medenica, Stepwise optimiz-ation approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design, J. Mass Spectrom. 48 (2013) 875–884.

H.T. Bjorkman, P.O. Edlund, S.P. Jacobsson, Sonic spray ionization interface for liquid chromatography–mass spectrometry, Anal. Chim. Acta 468 (2002) 263–274.

N. Garcia-Villar, J. Saurina, S. Hernandez-Cassou, High-performance liquid chromatographic determination of biogenic amines in wines with an experimental design optimization procedure, Anal. Chim. Acta 575 (2006) 97–105.

E. Carasek, E. Cudjoe, J. Pawliszyn, Fast and sensitive method to determine chloroanisoles in cork using an internally cooled solid-phase microextraction fiber, J. Chromatogr., A 1138 (2007) 10–17.

E. Carasek, J. Pawliszyn, Screening of Tropical Fruit Volatile Compounds Using Solid-Phase Microextraction (SPME) Fibers and Internally Cooled SPME Fiber, J. Agr. Food Chem. 54 (2006) 8688–8696.

K. Zarei, M. Atabati, H. Ilkhani, Catalytic adsorptive stripping voltammetry determination of ultra trace amount of molybdenum using factorial design for optimization, Talanta 69 (2006) 816–821.

C.R.T. Tarley, L.T. Kubota, Molecularly-imprinted solid phase extraction of catechol from aqueous effluents for its selective determination by differential pulse voltammetry, Anal. Chim. Acta 548 (2005) 11–19.

R.F. Teofilo, E.L. Reis, C. Reis, G.A. da Silva, L.T.Kubota, Experimental Design Employed to Square Wave Voltammetry Response Optimization for the Glyphosate Determination, J. Brazil. Chem. Soc. 15 (2004) 865–871.

C.R.T. Tarley, M.G. Segatelli, L.T. Kubota, Amperometric determination of chloroguaiacol at submicromolar levels after on-line preconcentration with molecularly imprinted polymers, Talanta 69 (2006) 259–266.

M.L. Felsner, C.B. Cano, J.R. Matos, L.B. de Almeida-Muradian, R.E. Bruns, Optimization of Thermogravimetric Analysis of Ash Content in Honey, J. Brazil. Chem. Soc. 15 (2004) 797–802.

A.B. Baranda, N. Etexbarria, R.M. Jimenez, R.M. Alonso, Development of a liquid–liquid extraction procedure for five 1,4-dihydropyridines calcium channel antagonists from human plasma using experimental design, Talanta 67 (2005) 933–941.

H. Ebrahimzadeh, Y. Yamini, F. Kamarei, S. Shariati, Homogeneous liquid–liquid extraction of trace amounts of mononitrotoluenes from waste water samples, Anal. Chim. Acta 594 (2007) 93–100.

E.R. Pereira-Filho, R.J. Poppi, M.A.Z. Arruda, Employment of factorial design for optimization of pirolisys and atomization temperatures for Al, Cd, Mo, and Pb determination by ETAAS, Quim. Nova 25 (2002) 246–253.

F.V. de Amorim, C. Bof, M.B. Franco, J.B.B. da Silva, C.C. Nascentes, Comparative study of conventional and multivariate methods for aluminum determination in soft drinks by graphite furnace atomic absorption spectrometry, Microchem. J. 82 (2006) 168–173.

M. Villaneuva, M. Catasus, E.D. Salin, M. Pomares, Study of mixed-matrix effects induced by Ca and Mg in ICP-AES, J. Anal. At. Spectrom. 15 (2000) 877–882.

L.C. Trevizan, E.C. Vieira, A.R.A. Nogueira, J.A. N´obrega, Use of factorial design for evaluation of plasma conditions and comparison of two liquid sample introduction systems for an axially viewed inductively coupled plasma optical emission spectrometer, Spectrochim. Acta, B 60 (2005) 575–581.

A. Woller, H. Garraud, J. Boisson, A.M. Dorthe, P. Fodor, O.F.X. Donard, Simultaneous speciation of redox species of arsenic and selenium using an anion-exchange microbore column coupled with a micro-concentric nebulizer and an inductively coupled plasma mass spectrometer as detector, J. Anal. At. Spectrom. 13 (1998) 141–149.

L. Zhang, C.M. Borror, T.R. Sandrin, A designed experi-ments approach to optimization of automated data acquisition during characterization of bacteria with MALDI-TOF mass spectrometry, PLoS One 9 (2014) e92720–92731.

K.H. Liland, B.H. Mevik, E.O. Rukke, T. Almoy, M. Skaugen, Tomas Isaksson, Quantitative whole spectrum analysis with MALDI-TOF MS, Part I: measurement optimization, Chem. Intell. Lab. Syst. 96 (2009) 210–218.

H. Brandt, T. Ehmann, M. Otto, Toward Prediction: Using Chemometrics for the Optimization of Sample Preparation in MALDI-TOF MS of Synthetic Polymers, Anal. Chem. 82 (2010) 8169–8175.

J.D. Badía, E. Strömberg, A. Ribes-Greus, S. Karlsson, A statistical design of experiments for optimizing the MALDI-TOF-MS sample preparation of polymers. An application in the assessment of the thermo-mechanical degradation mechanisms of poly (ethylene terephthalate), Anal. Chim. Acta 692 (2011) 85–95.

M.A.R. Meier, N. Adams, U.S. Schubert, Statistical approach to understand MALDI-TOFMS matrices: disco-very and evaluation of new MALDI matrices, Anal. Chem. 79 (2007) 863–869.

N. Al Masoud, E. Correa, D.K. Trivedi, R. Goodacre, Fractional Factorial Design of MALDI-TOF-MS Sample Preparations for the Optimized Detection of Phospholipids and Acylglycerols, Anal. Chem. 88 (2016) 6301–6308.

G.M. Intille, C.E. Pfluger, W.A. Baker, Crystal and molecular structure of chloro(2,2′,2″-terpyridine)palladium(II) chloride dihydrate, C15H15Cl2N3O2Pd, J. Cryst. Mol. Struct. 3 (1973) 47–54.

M. Petković, B. Petrović, J. Savić, Ž.D. Bugarčić, J. Dmitrić-Marković, T. Momić, V. Vasić, Flavonoids as matrices for MALDI-TOF mass spectrometric analysis of transition metal complexes, Int. J. Mass Spectrom. 290 (2010) 39–46.

S.L.C. Ferreira, R.E. Bruns, H.S. Ferreira, G.D. Matos, J.M. David,G.C. Brandao, E.G.P. da Silva, L.A. Portugal, P.S. dos Reis, A.S. Souza, W.N.L. dos Santos, Box–Behnken design: An alternative for the optimization of analytical methods, Anal. Chim. Acta 597 (2007) 179–186.

DOI: http://dx.doi.org/10.2298/HEMIND160614038R


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