Electrospray ionization matrix effects

It is well known that electrospray ionization (El) suffers from suppression effects when polar/ionic compounds other than the analyte(s) of interest, such as those originating from the sample matrix, are present, with this phenomenon being attributed to competitive ionization of all of the appropriate species present [33]. Matrix effects can, therefore, be considerable and these have two distinct implications for quantitative procedures, as follows ... 

The fact that APCl and electrospray are soft ionization techniques is often advantageous because the molecular ion alone, in conjunction with HPLC separation, often provides adequate selectivity and sensitivity to allow an analytical method to be developed. Again, method development is important, particularly when more than one analyte is to be determined, when the effect of experimental parameters, such as pH, flow rate, etc., is not likely to be the same for each. Electrospray, in particular, is susceptible to matrix effects and the method of standard additions is often required to provide adequate accuracy and precision. 

The method for chloroacetanilide soil metabolites in water determines concentrations of ethanesulfonic acid (ESA) and oxanilic acid (OXA) metabolites of alachlor, acetochlor, and metolachlor in surface water and groundwater samples by direct aqueous injection LC/MS/MS. After injection, compounds are separated by reversed-phase HPLC and introduced into the mass spectrometer with a TurboIonSpray atmospheric pressure ionization (API) interface. Using direct aqueous injection without prior SPE and/or concentration minimizes losses and greatly simplifies the analytical procedure. Standard addition experiments can be used to check for matrix effects. With multiple-reaction monitoring in the negative electrospray ionization mode, LC/MS/MS provides superior specificity and sensitivity compared with conventional liquid chromatography/mass spectrometry (LC/MS) or liquid chromatography/ultraviolet detection (LC/UV), and the need for a confirmatory method is eliminated. In summary,... 

Electrospray ionization (ESI) and APCI are the two popular API techniques that will be discussed here. The applications to the analysis of pesticides that will be discussed include imidazolinone herbicides, phenoxy acid herbicides, and A-methyl carbamate insecticides. Matrix effects with respect to quantitation also will be discussed. Eor the... 

Tesche, F. Pickard, V. Matrix effects during analysis of plasma samples by electrospray and atmospheric pressure chemical ionization mass spectrometry practical approaches to their elimination. Rapid Commun Mass Spectrom 2003, 17, 1950—1957. 

ToF mass spectrometers as dynamic instruments gained popularity with the introduction of matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) as effective pulsed ion sources for the soft ionization of large biomolecules (up to 10s dalton) due to their high ion transmission.38 ToF mass spectrometers, quadrupole analyzers and/or magnetic sector fields can be combined in tandem mass spectrometers (MS/MS) for the analysis of organic compounds. 

A selective, sensitive, and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma [32], Donepezil was twice extracted from human plasma using methyl-ferf-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile ammonium formate (50 mM, pH 4.0) (85 15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/ ml and the lower limit of quantification was 0.1 ng/ml using 200 /d plasma sample. The CV and relative error for intra- and inter-assay at four quality control levels were 2.7% to 10.5% and —10.0% to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers. 

Kloepfer, A., J.B. Quintana, and T. Reemtsma. 2005. Operational options to reduce matrix effects in liquid chromatography-electrospray ionization-mass spectrometry analysis of aqueous environmental samples. 7. Chromatogr. A 1067 153-160. 

Zrostlikova J, Hajslova J, Poustka J, Begany P (2002) Alternative calibration approaches to compensate the effect of co-extracted matrix components in liquid chromatography-electrospray ionization tandem mass spectrometry analysis of pesticide residues in plant materials. J Chromatogr A 973 13-26... 

Ahnoff M, Wurzer A et al. (2003) Characterization of serum albumin and lysoPCs as major contributors to plasma sample matrix effects on electrospray ionization efficiency, Presented at the 2009 ASMS conference, Montreal, Canada... 

Pascoe R, Foley JP, Gusev Al (2001) Reduction in Matrix-Related Signal Suppression Effects in Electrospray Ionization Mass Spectrometry Using On-Line Two-Dimensional Liquid Chromatography. Analytical Chemistry 73 6014-6023... 

Hou W, Watters JW, McLeod HL (2004) Simple and rapid docetaxel assay in human plasma by protein precipitation and high-performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography B 804 263-267 Schuhmacher J, Zimmer D, Tesche F, Pickard V (2003) Matrix effects during analysis of plasma samples by electrospray and atmospheric pressure chemical ionization mass spectrometry practical approaches to their elimination. Rapid Communications in Mass Spectrometry 17 1950-1957 Shah PW (2001) Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services, Food and Drug Administration... 

One limitation of LC-MS/MS methodology is that compounds in the sample extract, typically lipids, can affect the initial ionization of the analyte. This is referred to as matrix effects and can either enhance or suppress the electrospray ionization, leading to considerable inaccuracies in both qualitative and quantitative analyses [96, 97]. As such, the cleanup methodology employed, especially when working with biological samples, is of the utmost importance. In addition, the use of mass-labelled internal standards and matrix-matched standards, can minimize matrix effects [93, 94]. 

Several recommendations arose from the interlaboratory smdy to minimize analytical challenges and to ensure data quality. As discussed above, it is recommended that mass labelled PFCs be employed as internal standards [93, 97]. It should be noted, however, that some electrospray ionization suppression may still occur if these internal standards are used at high concentrations [97]. Matrix effects can also be minimized by employing matrix-matched calibration standards in lieu of solvent-based calibration standards [97]. Unfortunately, matrix-matched standards can be impractical when an appropriate clean matrix cannot be found [94]. Other quality assurance and quality control measures, such as spike and recovery analyses of an analyte added to the sample matrix, repetitive analysis of samples to determine precision and comparison of internal standard quantitation to quantitation via standard additions, are also useful in determining data quality [94]. 

Enke, C.G. A Predictive Model for Matrix and Analyte Effects in Electrospray Ionization of Singly-Charged Ionic Analytes, Anal. Chem. 69,4885-4893 (1997). 

Marchi et al. [64] reported on the utility of various sample cleanup procedures for reducing the matrix effects that are caused by various plasma constituents. They found that the best sample preparation procedure was to use PPT followed by an online SPE system. The authors also stated that with this sample preparation procedure, atmospheric pressure photoionization (APPI) was the least affected by matrix effects, followed by atmospheric pressure chemical ionization (APCI) and then electrospray ionization (ESI). 

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