Method development aspects for the quantitation of pharmaceutical compounds in human plasma with a matrix‐assisted laser desorption/ionization source in the multiple reaction monitoring mode

Kovarik, Peter; Grivet, Chantal; Bourgogne, Emmanuel; Hopfgartner, Gérard

doi:10.1002/rcm.2912

Cited by 54 publications

(47 citation statements)

References 15 publications

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“…Kovaric and colleagues [35] also investigated aspects of the quantitative analysis of pharmaceutical compounds in human plasma based on MALD-TOF MS operated in the multiple reaction monitoring mode. Talinolol was selected as a model analyte in these studies and liquid-liquid extraction and protein precipitation were evaluated, both with and without chromatographic separation.…”

Section: Low Molecular Mass Analytesmentioning

confidence: 99%

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Duncan¹,

Röder²,

Hunsucker³

2008

Briefings in Functional Genomics and Proteomics

191

162

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This review summarizes the essential characteristics of matrix-assisted laser desorption/ionization (MALDI) timeof-flight mass spectrometry (TOF MS), especially as they relate to its applications in quantitative analysis. Approaches to quantification by MALDI-TOF MS are presented and published applications are critically reviewed.Keywords: quantification; quantitative analysis; MALDI; mass spectrometry; biomarkers OVERVIEWSince its inception in 1987 [1], matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS) has been applied for the analysis of a wide range of biomolecules. Initial applications were almost exclusively for the qualitative analysis of biopolymers because MALDI-TOF MS provided a fast and accurate approach to molecular mass and purity information: Is my material the right mass and is it free from contaminants? Because of the speed of analysis, ease of use, relative low equipment cost, ease of data interpretation and limited potential for cross-contamination between samples/users, MALDI-TOF MS systems were considered walk-up instruments where investigators run their own samples and determine, within minutes, whether they were on the right track with their work.There were, however, two specific areas of application where MALDI-TOF MS was initially viewed as impractical: i.e. the analysis of low mass analytes and quantitative applications. Low mass analysis is complicated by the vast molar excess of the matrix that can swamp any analyte-specific signal in the low m/z region of the spectrum. Quantitative analysis was viewed as implausible because crystallization does not yield a uniform distribution of the analyte and matrix across the target surface and this gives rise to regions where the analyte signal is especially intense relative to other locations on the target surface. MALDI MS was therefore viewed as inherently irreproducible because, for a given amount of analyte loaded onto the target, the measured ion intensity varies.Subsequently, it has been shown that both these perceived limitations can be overcome and quantification can be routine, both for low and high mass analytes. Now, an extensive list of published applications includes quantification of amino acids, lipids, natural products, drugs, polymers, herbicides, metabolites, toxins, oligonucleotides, carbohydrates, peptides and proteins. (Selected applications from these areas are discussed at the end of this review.) Here, we focus on the quantitative applications of MALDI and illustrate applications relating to both low and high-molecular mass analytes. We also discuss the strategies for applying MALDI to relative and absolute quantification. While MALDI is most commonly combined with TOF analysers, other analyser options are possible and applications employing these are also presented. Our aim is not to provide an exhaustive catalogue of published applications, but to discuss the general principles and to illustrate the

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Section: Low Molecular Mass Analytesmentioning

confidence: 99%

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Duncan¹,

Röder²,

Hunsucker³

2008

Briefings in Functional Genomics and Proteomics

191

162

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Section: Lc/esi-ms or Lc/apci-ms)mentioning

confidence: 99%

“…In others, however, extensive prior separation is not necessary, and it can be replaced by a simpler extraction step. In these cases, current highthroughput approaches include direct injection of the sample solution into the MS from a 96-well sample plate for analysis by API [2], or the spotting of solid samples with an organic matrix for analysis by matrix-assisted laser desorption/ionization (MALDI) [3].New options for the ionization of samples at atmospheric pressure have emerged recently. The family of ambient ionization methods for mass spectrometry, which originated with desorption electrospray ionization (DESI) [4] and direct analysis in real time (DART) [5], has rapidly expanded to include a number of new members including MALDESI, LAESI, PADI, ASAP, DBDI, and ELDI [6 -11].…”

mentioning

confidence: 99%

High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry

Manicke

Kistler

Ifa

et al. 2009

J. Am. Soc. Mass Spectrom.

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A newly developed high-throughput desorption electrospray ionization (DESI) source was characterized in terms of its performance in quantitative analysis. A 96-sample array, containing pharmaceuticals in various matrices, was analyzed in a single run with a total analysis time of 3 min. These solution-phase samples were examined from a hydrophobic PTFE ink printed on glass. The quantitative accuracy, precision, and limit of detection (LOD) were characterized. Chemical background-free samples of propranolol (PRN) with PRN-d 7 as internal standard (IS) and carbamazepine (CBZ) with CBZ-d 10 as IS were examined. So were two other sample sets consisting of PRN/PRN-d 7 at varying concentration in a biological milieu of 10% urine or porcine brain total lipid extract, total lipid concentration 250 ng/ L. The background-free samples, examined in a total analysis time of 1.5 s/sample, showed good quantitative accuracy and precision, with a relative error (RE) and relative standard deviation (RSD) generally less than 3% and 5%, respectively. The samples in urine and the lipid extract required a longer analysis time (2.5 s/sample) and showed RSD values of around 10% for the samples in urine and 4% for the lipid extract samples and RE values of less than 3% for both sets. The LOD for PRN and CBZ when analyzed without chemical background was 10 and 30 fmol, respectively. The LOD of PRN increased to 400 fmol analyzed in 10% urine, and 200 fmol when analyzed in the brain lipid extract. (J Am Soc Mass Spectrom 2009, 20, 321-325) © 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry Q uantitative analysis of pharmaceutical compounds in biological fluids is typically carried out using liquid chromatography separation combined with a mass spectrometer fitted with an atmospheric pressure ionization (API) ion source, usually electrospray ionization or atmospheric pressure chemical ionization (LC/ESI-MS or LC/APCI-MS). Such a system can analyze one sample for numerous components in a matter of a few minutes [1]. In most applications, the separation device is directly coupled on-line with the MS. In others, however, extensive prior separation is not necessary, and it can be replaced by a simpler extraction step. In these cases, current highthroughput approaches include direct injection of the sample solution into the MS from a 96-well sample plate for analysis by API [2], or the spotting of solid samples with an organic matrix for analysis by matrix-assisted laser desorption/ionization (MALDI) [3].New options for the ionization of samples at atmospheric pressure have emerged recently. The family of ambient ionization methods for mass spectrometry, which originated with desorption electrospray ionization (DESI) [4] and direct analysis in real time (DART) [5], has rapidly expanded to include a number of new members including MALDESI, LAESI, PADI, ASAP, DBDI, and ELDI [6 -11]. In DESI-MS, samples are analyzed by directing a pneumatically-assisted stream of charged microdroplets at the surface in the ambient...

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“…The matrix exhibits a strong absorption at the laser wavelength used (typically 337 nm or 355 nm in the UV), which, after irradiation with a short pulse of laser light, leads to the ablation of a shallow surface region into the vacuum of the mass spectrometer, the release of intact gaseous matrix and analyte molecules, and their partial ionization. Since its introduction in the 1980s, MALDI has found widespread use in the mass spectrometric analysis of biological macromolecules but recently also has been used increasingly for small-molecule analysis (5,6).…”

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confidence: 99%

4-Chloro-α-cyanocinnamic acid is an advanced, rationally designed MALDI matrix

Jaskolla

Lehmann

Karas

2008

Proc. Natl. Acad. Sci. U.S.A.

143

168

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Matrix-assisted laser desorption ionization (MALDI) has become an enabling technology for the fields of protein mass spectrometry (MS) and proteomics. Despite its widespread use, for example, in protein identification via peptide mass fingerprinting, a comprehensive model for the generation of free gas-phase ions has not yet been developed. All matrices in use today, such as ␣-cyano-4-hydroxycinnamic acid (CHCA), have been found empirically and stem from the early days of MALDI. By systematic and targeted variation of the functional groups of the ␣-cyanocinnamic acid core unit, 4-chloro-␣-cyanocinnamic acid (Cl-CCA) was selected and synthesized, and it exhibited outstanding matrix properties. Key features are a substantial increase in sensitivity and a considerably enhanced peptide recovery in proteomic analyses because of a much more uniform response to peptides of different basicity. Using Cl-CCA as a matrix for a 1 fmol bovine serum albumin (BSA) in-solution digest, the sequence coverage is raised to 48%, compared with 4% for CHCA. For a gel band containing 25 fmol of BSA, unambiguous protein identification becomes possible with Cl-CCA. These findings also imply ion formation via a chemical ionization mechanism with proton transfer from a reactive protonated matrix species to the peptide analytes. The considerable increase in performance promises to have a strong impact on future analytical applications of MALDI, because current sensitivity limits are overcome and more comprehensive analyses come into reach.ionization mechanism ͉ proton transfer M atrix-assisted laser desorption ionization (MALDI) (1-3) relies on a cocrystallization of the analytes of interest with an excess of small organic compounds, the matrix, which is accomplished by either simply drying Ϸ 1-l droplet of a solution containing matrix and analyte (dried-droplet preparation) (2, 3) or by depositing a droplet of the analyte solution onto a prespotted matrix layer (surface preparation) (4). The matrix exhibits a strong absorption at the laser wavelength used (typically 337 nm or 355 nm in the UV), which, after irradiation with a short pulse of laser light, leads to the ablation of a shallow surface region into the vacuum of the mass spectrometer, the release of intact gaseous matrix and analyte molecules, and their partial ionization. Since its introduction in the 1980s, MALDI has found widespread use in the mass spectrometric analysis of biological macromolecules but recently also has been used increasingly for small-molecule analysis (5, 6).However, the main field of application of MALDI mass spectrometry (MS) today is protein identification in proteomic schemes by using the peptide mass fingerprint (PMF) approach (7), often supplemented by MALDI-time-of-f light/time-offlight (TOF/TOF) analyses. ␣-Cyano-4-hydroxycinnamic acid (CHCA) (8) as a matrix (in positive-ion mode) allows the researcher to identify proteins via MS or MS/MS analysis of their proteolytic peptide products (typically generated by trypsin) and by using protein or DNA seque...

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Method development aspects for the quantitation of pharmaceutical compounds in human plasma with a matrix‐assisted laser desorption/ionization source in the multiple reaction monitoring mode

Cited by 54 publications

References 15 publications

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry

4-Chloro-α-cyanocinnamic acid is an advanced, rationally designed MALDI matrix

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