Chemometric Approach to Evaluate the Parameters Affecting Electrospray: Application of a Statistical Design of Experiments for the Study of Arginine Ionization

Abstract

The effects of different experimental parameters on arginine electrospray ionization have been investigated with response surface modeling design. This chemometric technique allows a study of the effects of selected experimental variables and their interactions on the response of an experiment by performing a limited number of analyses. Six variables were studied: methanol content in the liquid phase, formic acid concentration, electrospray voltage, orifice voltage, mobile phase flow rate, and sheath gas flow rate. Signal abundance and signal-to-noise ratio of the protonated molecule and the protonated dimer were measured from the electrospray mass spectra and these four responses were tested by the design. The factor that exhibits the greatest influence on MH⁺ abundance is shown to be the liquid flow rate whereas the formation of protonated dimers is mainly controlled by the percentage of methanol in the mobile phase. A strong synergic effect of methanol content and formic acid concentration in the liquid has also been demonstrated in the study of noise level. Moreover, the capabilities of the multicriteria optimization method have been demonstrated through the successful prediction of a set of optimal experimental conditions.

Keywords

electrospray ionization optimization response surface modeling design of experiments

Get full access to this article

View all access options for this article.

References

Hayati

Bailey

A.I.

Tadros

T.F.

, “Mechanism of Stable Jet Formation in Electrohydrodynamic Atomization”, Nature 319, 41 (1986).

Ikonomou

M.G.

Blades

A.T.

Kebarle

, “Electrospray Ion Spray—a Comparison of Mechanisms and Performance”, Anal. Chem. 63, 1989 (1991).

Kebarle

Tang

, “From Ions in Solution to Ions in the Gas-Phase—the Mechanism of Electrospray Mass-Spectrometry”, Anal. Chem. 65, 972A (1993).

Rayleigh

Lord

, “On the equilibrium of liquid conducting masses charged with electricity”, Philos. Mag. 14, 184 (1882).

Box

G.E.P.

Hunter

W.G.

Hunter

J.S.

, in Statistics for Experimenters: An Introduction to Design, Data Analysis and Model Building. John Wiley & Sons, New York, USA, pp. 306–313 (1978).

Fisher

R.A.

, The Design of Experiments. Oliver and Boyd, Edinburgh, UK (1935).

Montgomery

D. C.

, Design and Analysis of Experiments, 5th Edn. John Wiley & Sons, New York, USA (2000).

Haaland

P.D.

, Experimental Design in Biotechnology. Marcel Dekker. New York, USA (1989).

Tye

, “Application of statistical ‘design of experiments’ methods in drug discovery”, Drug Discov. Today 9, 485 (2004).

10.

Ferreira

S.L.C.

dos Santos

W.N.L.

Quintella

C.M.

Neto

B.B.

Bosque-Sendra

J.A.

, “Doehlert matrix: A chemometric tool for analytical chemistry – review”, Talanta 63, 1061 (2004).

11.

Hows

M.E.P.

Perrett

Kay

, “Optimisation of a simultaneous separation of sulphonamides, dihydrofolate reductase inhibitors and beta-lactam antibiotics by capillary electrophoresis”, J. Chrom. A 768, 97 (1997).

12.

Ragonese

Macka

Hughes

Petocz

, “The use of the Box–Behnken experimental design in the optimisation and robustness testing of a capillary electrophoresis method for the analysis of ethambutol hydrochloride in a pharmaceutical formulation”, J. Pharmaceut. Biomed. Anal. 27, 995 (2002).

13.

Grover

Decouzon

Maria

P.C.

Gal

J.F.

, “Reliability of Fourier transform ion cyclotron resonance determinations of rate constants for ion molecule reactions”, Eur. Mass Spectrom. 2, 213 (1996).

14.

Carpignano

Operti

Rabezzana

Vaglio

G.A.

, “Chemometric approach to evaluate the parameters affecting the determination of reaction rate constants by ion trap a lass spectrometry”, J. Am. Soc. Mass Spectrom. 9, 938 (1998).

15.

Gal

J.F.

Maria

P.C.

Operti

Rabezzana

Vaglio

G.A.

, “A quadrupole ion trap and Fourier transform ion cyclotron resonance concerted study of the kinetics of an ion/molecule association reaction: A chemometric approach”, Eur. J. Mass Spectrom. 9, 435 (2003).

16.

Moberg

Markides

K.E.

Bylund

, “Multi-parameter investigation of tandem mass spectrometry in a linear ion trap using response surface modeling”, J. Mass Spectrom. 40, 317 (2005).

17.

Riter

L.S.

Vitek

Gooding

K.M.

Hodge

B.D.

Julian

R.K.

, “Statistical design of experiments as a tool in mass spectrometry”, J. Mass Spectrom. 40, 565 (2005).

18.

Zhang

D.X.

L.M.

Koch

K.J.

Cooks

R.G.

, “Arginine clusters generated by electrospray ionization and identified by tandem mass spectrometry”, Eur. J. Mass Spectrom. 5, 353 (1999).

19.

Meng

C.K.

Fenn

J.B.

, “Formation of Charged Clusters During Electrospray Ionization of Organic Solute Species”, Org. Mass Spectrom. 26, 542 (1991).

20.

Derringer

Suich

, “Simultaneous optimization of several response variables”, J. Qual. Technol. 12, 214 (1980).

21.

Mathieu

Nony

Phan-Tan-Luu

, NEMROD®-W (New Efficient Methodology for Research using Optimal Design), LPRAI SARL, Marseille, France (2000).

22.

Box

G.E.P.

Behnken

D.W.

, “Some new three level designs for the study of quantitative variables”, Technometrics 2, 455 (1960) .

23.

Tang

Kebarle

, “Effect of the Conductivity of the Electrosprayed Solution on the Electrospray Current—Factors Determining Analyte Sensitivity in Electrospray Mass-Spectrometry”, Anal. Chem. 63, 2709 (1991).

24.

Chowdhury

S.K.

Chait

B.T.

, “Method for the Electrospray Ionization of Highly Conductive Aqueous-Solutions”, Anal. Chem. 63, 1660 (1991).

25.

Hao

C.Y.

March

R.E.

, “Electrospray ionization tandem mass spectrometric study of salt cluster ions: Part 2—Salts of polyatomic acid groups and of multivalent metals”, J. Mass Spectrom. 36, 509 (2001).

26.

Charles

Pepin

Gonnet

Tabet

J.C.

, “Effects of liquid phase composition on salt cluster formation in positive ion mode electrospray mass spectrometry: Implications for clustering mechanism in electrospray”, J. Am. Soc. Mass Spectrom. 12, 1077 (2001).

27.

Charles

Chiron

Galy

J.P.

, “Characterization of ammonium chloride derivatives by salt clustering in electrospray mass spectrometry”, Rapid Commun. Mass Spectrom. 17, 2471 (2003).